bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant Effects of Sophora davidi (Franch.) Skeels on d–Galactose–Induced Aging Model in Mice via Activating the SIRT1/p53 Pathway
Authors: Lin Beibei , Xu Dingqiao , Wu Sanqiao , Qi Shanshan , Xu Youmei , Liu Xiang , Zhang Xiaoying , Chen Chen
Published: December 2021

This study investigated the protective effect of Sophora davidi (Franch.) Skeels fruits extract (SDE) on d–galactose–induced acute aging in mice. Ultra performance liquid chromatography coupled with tine-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to identify the composition of compounds in SDE. KM mice were divided stochastically into the normal control group (NC, saline), d–galactose (D-gal) model group, vitamin C (Vc) group (positive control), low–, medium–and high–dose SDE treat groups. After 28 days administration and fasting overnight, the serum, liver, and brain samples of mice were collected. The levels of inducible nitric oxide synthase (iNOS), acetylcholinesterase (AChE) activity in the brain, malondialdehyde (MDA) and reduced glutathione (GSH) content, superoxide dismutase (SOD) and total antioxidant capacity (T–AOC) activity in the liver and brain were measured. Immunohistochemistry was applied to detect silent information regulator 1 (SIRT1) and p53 protein expression in the liver and brain, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of nuclear factor κB (NF–κB), tumor necrosis factor (TNF–α), interleukin–6 (IL–6), interleukin-1β (IL–1β), and anti-aging factor Klotho in the liver and brain. The results showed that UPLC-Q-TOF/MS identified 78 compounds in SDE. SDE could reduce the iNOS activity in serum and AChE activity in the brain, upregulate the levels of SOD, T–AOC and GSH in liver and brain, and debase the MDA content in liver and brain. SDE could downregulate the mRNA expressions of TNF–α, NF–kB, IL–1β, and IL–6 in the liver and brain, and elevate the mRNA expression of Klotho. SDE improved the pathological changes of the liver and brain induced by D–gal, increased the expression of SIRT1 protein in the liver and brain, and inhibited the expression of p53 protein induced by D–gal. To summarize, SDE demonstrated clear anti–aging effect, and its mechanism may be relevant to the activation of the SIRT1/p53 signal pathway.
Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment
Authors: Wang Cong , Lin Jinyi , Wang Yan , Hsi David H. , Chen Jiahui , Liu Tianshu , Zhou Yuhong , Ren Zhenggang , Zeng Zhaochong , Cheng Leilei , Ge Junbo
Published: December 2021

Background: Immune checkpoint inhibitor (ICI)–associated myocarditis is an uncommon and potentially fatal immune-related adverse event (irAE). Although corticosteroids are recommended as the first-line treatment by current guidelines, patients still have variable responses to it, and the guidelines vary significantly in terms of treatment strategies.

Objectives: In this study, we performed a retrospective analysis of ICI-associated myocarditis in our hospital to propose a new comparative analysis to aid individualized treatment.

Methods: We reviewed detailed records of 24 patients with confirmed ICI-associated myocarditis in our hospital from July 1, 2019, to April 1, 2021. Although all the cases in our study received recommended initial corticosteroid treatment according to the guidelines, different responses to corticosteroid were observed during the process of subsequent corticosteroid tapering. Basing on troponin cardiac troponin T rebound during corticosteroid tapering, we propose a new classification analysis of ICI-associated myocarditis that included two subgroups: corticosteroid-sensitive (n = 8) and corticosteroid-resistant group (n = 16).

Results: Compared with corticosteroid-sensitive patients, larger doses of corticosteroid, longer period of treatment, and higher mortality rate were found in corticosteroid-resistant patients. Corticosteroid-resistant patients were characterized by more prominent ptosis, muscle weakness, elevated cardiac biomarkers, creatine kinase, and hepatic enzymes levels than that in the corticosteroid-sensitive patients. Tofacitinib (5 mg twice a day) was used in 11 corticosteroid-resistant patients, with seven patients recovered from ICI-associated myocarditis, showing a promising therapeutic effect.

Conclusion: Our group analysis of corticosteroid responsiveness in patients with ICI-associated myocarditis may help clinicians to apply individualized treatment in this high-risk cohort. In addition, tofacitinib could provide clinical benefits when used early in the corticosteroid-resistant patients and may provide a new option for the treatment of ICI-associated myocarditis.
Sonodynamic Effects of a Novel Ether-Group Modified Porphyrin Derivative Combined With Pulsed Low-Intensity Ultrasound on PC-9 Cells
Authors: Jin Yinghua , Zhou Qi , Geng Jianxiong , Meng Qingwei , Wei Zixin , Ding Meijuan , Zhou Jing , Zeng Yuan , Cao Wenwu , Liu Fang , Yu Yan
Published: December 2021

Sonodynamic therapy (SDT) is a developing modality for cancer treatment based on the synergistic effect of ultrasound and chemical compounds which are known as sonosensitizers. The development of more efficient sonosensitizers has become an urgent issue in this field. In this study, a novel porphyrin derivative (BBTPP) mediated SDT was evaluated on PC-9 cells. Pulsed low-intensity ultrasound (PLIU) was used for its little thermal and mechanical damage. The accumulation of drugs in cells was evaluated through porphyrin fluorescence, and the cytotoxicity of BBTPP was evaluated using a cell counting kit-8 assay. The sonodynamic effect was investigated by Hoechst 33342/PI and Annexin V-FITC/PI double staining, which showed an apoptotic rate of 18.87% in the BBTPP-SDT group, as compared with 1.71%, 1.4%, 1.57%, 3.61%, 11.18% in the control, BBTPP, hematoporphyrin monomethyl ether (HMME), ultrasound, and HMME-SDT groups, respectively. The sono-toxic effect of BBTPP was significantly superior to HMME. Our results showed that BBTPP-SDT resulted in much higher intracellular reactive oxygen species (ROS) and lipid peroxidation levels which were evaluated by 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) and Liperfluo assay, respectively. The expressions of Bax, Bcl-2, caspase-9, caspase-8, and cleaved caspase-3 proteins were evaluated to investigate the apoptotic mechanism of BBTPP-SDT. The results of this study showed that the combination of BBTPP and PLIU induced the generation of ROS, resulting in lipid peroxidation, and activated both the extrinsic and intrinsic apoptotic pathways of PC-9 cells. Our results also suggested that the ether group introduced in the side chain of porphyrin could enhance the sono-toxicity of porphyrin-based sensitizers under the sonication of PLIU. These results supported the possibility of BBTPP as a promising sonosensitizer, and an appropriate side chain could enhance the sono-sensitivity of porphyrins.
Redox Properties of Human Erythrocytes Are Adapted for Vitamin C Recycling
Authors: Eigenschink Michael , Savran Danylo , Zitterer Christoph P. , Granitzer Sebastian , Fritz Magdalena , Baron David M. , Müllner Ernst W. , Salzer Ulrich
Published: December 2021

Ascorbic acid (AA; or vitamin C) is an important physiological antioxidant and radical scavenger. Some mammalian species, including homo sapiens, have lost the ability to synthetize AA and depend on its nutritional uptake. Erythrocytes from AA-auxotroph mammals express high amounts of the glucose transporter GLUT1. This isoform enables rapid uptake of glucose as well as dehydroascorbate (DHA), the fully oxidized form of AA. Here, we explored the effects of DHA uptake on the redox metabolism of human erythrocytes. DHA uptake enhanced plasma membrane electron transport (PMET) activity. This process is mediated by DCytb, a membrane bound cytochrome catalyzing extracellular reduction of Fe3+ and ascorbate free radical (AFR), the first oxidized form of AA. DHA uptake also decreased cellular radical oxygen species (ROS) levels. Both effects were massively enhanced in the presence of physiological glucose concentrations. Reduction of DHA to AA largely depleted intracellular glutathione (GSH) and induced the efflux of its oxidized form, GSSG. GSSG efflux could be inhibited by MK-571 (IC50 = 5 μM), indicating involvement of multidrug resistance associated protein (MRP1/4). DHA-dependent GSH depletion and GSSG efflux were completely rescued in the presence of 5 mM glucose and, partially, by 2-deoxy-glucose (2-DG), respectively. These findings indicate that human erythrocytes are physiologically adapted to recycle AA both intracellularly via GLUT1-mediated DHA uptake and reduction and extracellularly via DCytb-mediated AFR reduction. We discuss the possibility that this improved erythrocyte-mediated AA recycling was a prerequisite for the emergence of AA auxotrophy which independently occurred at least twice during mammalian evolution.
Occurrence of Side Effects in Treatment-Resistant Depression: Role of Clinical, Socio-Demographic and Environmental Characteristics
Authors: Levy Anna , El-Hage Wissam , Bennabi Djamila , Allauze Etienne , Bouvard Alexandra , Camus Vincent , Courtet Philippe , Dorey Jean-Michel , Etain Bruno , Fond Guillaume , Genty Jean-Baptiste , Holtzmann Jérôme , Horn Mathilde , Leboyer Marion , Llorca Pierre-Michel , Meyrel Manon , Molière Fanny , Nguon Anne-Sophie , Petrucci Jean , Rey Romain , Richieri Raphaelle , Stephan Florian , Vaiva Guillaume , Walter Michel , Haffen Emmanuel , Aouizerate Bruno , Yrondi Antoine
Published: December 2021

Introduction: Treatment-resistant depression (TRD) is a disabling psychiatric condition characterized by the failure of two antidepressants (ADs). Since the occurrence of side effects (SEs) appears to be one of the main determinants of early discontinuation of pharmacological treatments contributing to a pseudo-resistance, the purpose of this study was to determine the parameters associated with the occurrence of SEs under ADs in a cohort of patients with TRD.

Methods: An observational, cross-sectional, multicentre study was carried out using data from the French network of Expert Centers for TRD. For the 108 patients enrolled in the study, the statistical analyses focused on the overall occurrence and on the profile of the SEs (9 categories, 32 items).

Results: SEs were influenced by age and sex and were positively associated with the intensity of anxious, depressive and suicidal symptoms, a history of childhood trauma (sexual abuse, emotional abuse and neglect), and negatively associated with self-esteem, and assessment of overall functioning.

Conclusion: Using variables accessible in common practice, these results fall within the dynamic of a more tailored approach to medicine that could allow, through integrated pharmacological management, the continuation of antidepressant treatments, and therefore limit the risk of therapeutic failure.
Assessment of Knowledge, Attitudes, and Factors Influencing the Selection Student of Generic Medicine
Authors: Al-Arifi Mohamed N.
Published: December 2021

Background: Generic replacements for branded medicines have become a typical practice among registered pharmacists all over the world. Therefore, this study was aimed to determine the influence of the knowledge and attitudes of PharmD students and other factors on the selection of unbranded medicines.

Methods: A descriptive, cross-sectional study was conducted through Google Forms to collect data using self-reported questionnaires. The data was collected over a period of 3 months, from January to March 2021, among junior level pharmacy students who are currently undertaking a PharmD course at the King Saud University, College of Pharmacy, Riyadh, Saudi Arabia.

Results: The mean age of the students was 21.05± (SD = 1.03), majority of students 70.2% (n = 134) were able to define the term generic medicine, and about 65% (n = 123) were able to correctly define bioequivalence. More than half of the students, 56.5% (n = 108) lacked knowledge about the pharmacokinetic parameters of generic products. Meanwhile, the majority, 85% (n = 122), supported generics over branded medicines, and about 66% (n = 99) agreed that wider use of generic medicines would lead to less money required for the research and development of new pharmaceuticals.

Conclusion: Findings revealed that most pharmacy students possess sufficient knowledge of generic medicines, although knowledge in some aspects remains lacking.
Novel 60 GHz Band Spatial Synthetic Exposure Setup to Investigate Biological Effects of 5G and Beyond Wireless Systems on Human Body
Authors: Hikage Takashi , Ozaki Ryunosuke , Ishitake Tatsuya , Masuda Hiroshi
Published: December 2021

The global spread of 5th generation (5G) wireless systems causes some concern about health effects of millimeter waves (MMW). To investigate biological effects of local exposure to 5G-MMW on human body, a novel 60 GHz band exposure setup was developed, and its performance was validated. A spatial synthetic beam-type exposure setup using two dielectric lens antennas was proposed to achieve high intensity 60 GHz irradiation to the target area of human skin. Variety distributions and intensities of electromagnetic fields at the exposed area, which is modified by incident angles of the combined beams, were simulated using finite-difference time-domain methods. The exposure performance we estimated was verified by temperature elevations of surface in a physical arm-shaped silicone phantom during the MMW exposure. The interference fringes generated in the exposed area due to the combined two-directional beam radiations were observed both in the simulation and in the phantom experiment but eliminated by applying an orthogonalizing polarized feeding structure. Under these exposure conditions, the local temperature changes, which could evoke warmth sensations, were obtained at the target area of the human forearm skin, which means the achievement of exposure performance we intended.
Nutritional Status and Body Composition in Patients Suffering From Chronic Respiratory Diseases and Its Correlation With Pulmonary Rehabilitation
Authors: Wouters Emiel F. M.
Published: December 2021

As part of an individualized intervention to improve the physical, emotional, and social functioning of patients with chronic respiratory diseases in general and chronic obstructive pulmonary disease in particular, awareness of the presence and consequences of changes in body composition increased enormously during the last decades, and nutritional intervention is considered as an essential component in the comprehensive approach of these patients. This review describes the prevalence and the clinical impact of body composition changes and also provides an update of current intervention strategies. It is argued that body composition, preferentially a three-component evaluation of fat, lean, and bone mass, must become part of a thorough assessment of every patient, admitted for pulmonary rehabilitation.
Appropriateness of Outpatient Antibiotic Use in Seniors across Two Canadian Provinces
Authors: Saatchi Ariana , Reid Jennifer N. , Povitz Marcus , Shariff Salimah Z. , Silverman Michael , Morris Andrew M. , Reyes Romina C. , Patrick David M. , Marra Fawziah
Published: December 2021

Antimicrobials are among the most prescribed medications in Canada, with over 90% of antibiotics prescribed in outpatient settings. Seniors prescribed antimicrobials are particularly vulnerable to adverse drug events and antimicrobial resistance. The extent of inappropriate antibiotic prescribing in outpatient Canadian medical practice, and the potential long-term trends in this practice, are unknown. This study is the first in Canada to examine prescribing quality across two large-scale provincial healthcare systems to compare both quantity and quality of outpatient antibiotic use in seniors. Population-based analyses using administrative health databases were conducted in British Columbia (BC) and Ontario (ON), and all outpatient, oral antimicrobials dispensed to seniors (≥65 years) from 1 January 2000 to 31 December 2018 were identified. Antimicrobials were linked to an indication using a 3-tiered hierarchy. Tier 1 indications, which always require antibiotics, were given priority, followed by Tier 2 indications that sometimes require antibiotics, then Tier 3, which never require antibiotics. Prescription rates were calculated per 1000 population, and trends were examined overall, by drug class, and by patient demographics. Prescribing remained steady in both provinces, with 11,166,401 prescriptions dispensed overall in BC, and 27,656,014 overall in ON. BC prescribed at slightly elevated rates (range: 790 to 930 per 1000 residents), in comparison to ON (range: 745 to 785 per 1000 residents), throughout the study period. For both provinces, a Tier 3 diagnosis was the most common reason for antibiotic use, accounting for 50% of all indication-associated antibiotic prescribing. Although Tier 3 indications remained the most prescribed-for diagnoses throughout the study period, a declining trend over time is encouraging, with much room for improvement remaining. Elevated prescribing to seniors continues across Canadian outpatient settings, and prescribing quality is of high concern, with 50% of all antimicrobials prescribed inappropriately for common infections that do not require antimicrobials.
An Innovative Steel Damper with a Flexural and Shear–Flexural Mechanism to Enhance the CBF System Behavior: An Experimental and Numerical Study
Authors: Ghamari Ali , Almasi Behroz , Kim Chang-hyuk , Jeong Seong-Hoon , Hong Kee-Jeung
Published: December 2021

An innovative passive energy damper is introduced and studied experimentally and numerically. This damper is designed as the main plate for energy absorption which is surrounded by an octagon cover. In addition to simplicity in construction, it can be easily replaced after a severe earthquake. Experimental test results, as well as finite element results, indicated that, by connecting the cross-flexural plate to the main plate, the mechanism of the plate was changed from flexural to shear. However, the cross_flexural plate always acts as a flexural mechanism. Changing the shear mechanism to a flexural mechanism, on the other hand, increased the stiffness and strength, while it reduced the ultimate displacement. Comparing the hysteresis curve of specimens revealed that models without cross_flexural plates had less strength and energy_dissipating capability than other models. Adding the flexural plate to the damper without connecting to the main plate improved the behavior of the damper, mainly by improving the ultimate displacement. Connecting the cross plate to the web plate enhanced the ultimate strength and stiffness by 84% and 3.9, respectively, but it reduced the ductility by 2.25. Furthermore, relationships were proposed to predict the behavior of the dampers with high accuracy.
Wearable Sensory Apparatus for Real-Time Feedback in Wearable Robotics
Authors: Munih Marko , Ivanić Zoran , Kamnik Roman
Published: December 2021

We describe the Wearable Sensory Apparatus (WSA) System, which has been implemented and verified in accordance with the relevant standards. It comprises the Inertial Measurement Units (IMUs), real-time wireless data transmission over Ultrawideband (UWB), a Master Unit and several IMU dongles forming the Wireless Body Area Network (WBAN). The WSA is designed for, but is not restricted to, wearable robots. The paper focuses on the topology of the communication network, the WSA hardware, and the organization of the WSA firmware. The experimental evaluation of the WSA incorporates the confirmation of the timing using the supply current WSA profile, measurements related to determining the less error prone position of the master device on the backpack, measurements of the quality of the data transfer in a real environment scenario, measurements in the presence of other microwave signals, and an example of raw IMU signals during human walking. Placement of the master device on the top of the backpack was found to be less error prone, with less than 0.02% packet loss for all the IMU devices placed on different body segments. The packet loss did not change significantly in public buildings or on the street. There was no impact of Wi-Fi bands on the WSA data transfer. The WSA hardware and firmware passed conformance testing in a certified lab. Most importantly, the WSA performed reliably in the laboratory and in clinical tests with exoskeletons and prostheses.
Experimental and Numerical Investigations on Fire-Resistance Performance of Precast Concrete Hollow-Core Slabs
Authors: Heo Inwook , Darkhanbat Khaliunaa , Han Sun-Jin , Choi Seung-Ho , Jeong Hoseong , Kim Kang Su
Published: December 2021

In this study, full-scale fire tests and finite element (FE) analyses are conducted to investigate the fire resistance performance of hollow-core slabs (HCSs) manufactured using the extrusion method. The deflection of the HCS specimens and the temperature distribution in the section according to the fire exposure time are measured and analyzed comprehensively, and the test results are compared with the FE analysis results. In addition, parametric analyses are conducted on 21 cases with the HCS depth, span length, hollow ratio in a section, cover thickness of concrete, and load ratio (i.e., the ratio of the external load to the ultimate load) as variables, based on which the fire resistance performance of the HCS according to each variable is investigated. The analysis results show that the load ratio is a key factor governing the fire resistance behavior of HCSs, whereas the effects of the cover thickness of concrete and the hollow ratio in a section are relatively slight within the range of variables examined in this study.
Young Shoots and Mature Red Cabbage Inhibit Proliferation and Induce Apoptosis of Prostate Cancer Cell Lines
Authors: Drozdowska Mariola , Leszczyńska Teresa , Piasna-Słupecka Ewelina , Domagała Dominik , Koronowicz Aneta
Published: December 2021

Prostate cancer is one of the most common cancers in men. Recent dietary and epidemiological studies have suggested the benefit of dietary intake of cruciferous vegetables in lowering the incidence of cancer. The health promoting effects of red cabbage are attributed to their mixture of phytochemicals known for their antioxidant and anticancer activity. In the current study, we investigated whether young shoots and mature red cabbage had any effect on prostate cancer cell lines (DU145 and LNCaP). Attempts were also made to identify the potential molecular mechanism(s) by which plant material elicits its biological effects on prostate cancer cell lines. Here we report that the studied vegetable inhibited the proliferation of cancer cells and that this process was associated with the induction of apoptosis via caspase-dependent and both extrinsic and intrinsic pathways. In addition, we also observed the regulation of genes and proteins associated with cell survival and apoptotic events.
Variations in Concentrations and Ratio of Soluble Forms of Nutrients in Atmospheric Depositions and Effects for Marine Coastal Areas of Crimea, Black Sea
Authors: Varenik Alla V. , Konovalov Sergey K.
Published: December 2021

Atmospheric depositions have been recently recognized as an important source of nutrients for off-shore marine systems, in line with the coastal input and physical exchange. The input of nutrients with atmospheric depositions can change their inventory and ratio in the euphotic zone, thus increase the rate of primary production and the type of predominant phytoplankton. The influence of atmospheric depositions, temporal variations of this influence and consequences of this deposition have been neglected. Monitoring of nutrients in atmospheric depositions of Crimea in 2015–2020 has allowed studying of multi-scale variations in their input to coastal areas and scaling the effects of this input. It has been found that the contribution of dry deposition in the total flux of nutrients is more significant for silicates and phosphates. Intra-annual variations in concentrations of nitrogen reveal a maximum in an urbanized area for the cold period of year, due to burning of extra fuel. On the contrary, increasing concentrations of nitrogen have been detected in a rural area in warm period. High values of concentrations of phosphorus and silica are typical for dry summer period and associated with dust transport from natural and anthropogenic sources. The N:P:Si ratio in the atmospheric depositions has been significantly shifted towards nitrogen as compared to the stoichiometric ratio. The results obtained in this work suggest that additional flux of nutrients with atmospheric depositions is minor at the annual scale, but it may change the local inventory and C:N:P ratio in the surface layer of the sea on a daily-time scale. The input of nutrients with atmospheric depositions can lead to additional (up to twofold) production of organic matter and result in additional oxygen consumption, when this surplus organic matter sinks and is oxidized, thus supporting suboxic conditions in near-shore areas.
Comparative Analysis of Collagen-Containing Waste Biodegradation, Amino Acid, Peptide and Carbohydrate Composition of Hydrolysis Products
Authors: Sukhikh Stanislav , Noskova Svetlana , Ivanova Svetlana , Ulrikh Elena , Izgaryshev Alexsander , Larichev Timothy , Kozlova Oksana , Prosekov Alexander , Babich Olga
Published: December 2021

This paper aimed to study the biodegradation of collagen-containing waste (pork skin) induced by collagenase and Neutrase 1.5 MG enzymes and compare the amino acid, peptide, and carbohydrate composition of hydrolysis products. It was found that the degree of biodegradation of collagen-containing raw materials (pork skin) reached 78% when using an enzyme preparation (collagenase with a concentration of 250 U/g of the substrate) at pH 7.0, 40 °C, and a 360 min process duration. It was shown that the content of peptides with a molecular weight of 6.5–14.0 kDa in the hydrolysis products (collagenase) of collagen-containing wastes was 13.4 ± 0.40%, while in the products of hydrolysis (Neutrase 1.5 MG) it was 12.8 ± 0.38%. The study found that the hydrolysis products (Neutrase 1.5 MG) of collagen-containing raw materials contain fewer hexoses, free hexosamines, and hyaluronic acid than the hydrolysis products (collagenase) of collagen-containing raw materials. The content of chondroitin sulfates is practically the same in all samples of hydrolysis products. Proteases with collagenolytic activity are widely used in industry. Recently, they have increasingly been used in pharmaceutical, food, and other industries. Collagenases are promising enzymes for the production of chondroprotectors used for the treatment of osteoarthritis.
The Use of Tranexamic Acid in Anterior Cruciate Ligament Reconstruction: A Systematic Review
Authors: Prejbeanu Radu , Mioc Mihail Lazar , Deleanu Bogdan , Balanescu Andrei , Al Qatawneh Musab , Malita Daniel
Published: December 2021

Background: There are several papers that investigate the use of tranexamic acid (TXA) in anterior cruciate ligament reconstructions (ACLR) or other arthroscopic procedures that show favorable results and little to no complications. We aimed to perform a systematic review of all published randomized controlled trials (RCTs) that wanted to determine the effectiveness of intravenous use of TXA in ACLR. Methods: Data collection was performed independently by two authors via a previously created spreadsheet. They extracted information such as: first author name, publication year, lot size, TXA protocol, surgical protocol, outcome measures and follow-up duration. Results: After applying the screening process and the inclusion criteria, we were left with a total six RCTs. The selected studies included a total of 699 randomized patients. Statistical significance regarding a lower pain score (VAS) in the intervention groups was mostly reported for the early postoperative period (2 weeks). A statistically significant decrease in hemarthrosis grade was reported for the first 2–3 weeks. Conclusions: in our study, we show that TXA use in arthroscopic ACLR decreases postoperative blood loss and pain. Some evidence of improvement in functional scores was observed, but we believe that this needs to be addressed in specific long-term result studies.
Cooperative Buffering Schemes for Time-Shifted Live Streaming of Distributed Appliances
Authors: Kim Eunsam , Cho Yunho , Shin Hyoseop
Published: December 2021

Distributed appliances connected to the Internet have provided various multimedia services. In particular, networked Personal Video Recorders (PVRs) can store broadcast TV programs in their storage devices or receive them from central servers, enabling people to watch the programs they want at any desired time. However, the conventional CDNs capable of supporting a large number of concurrent users have limitations in scalability because more servers are required in proportion to the increased users. To address this problem, we have developed a time-shifted live streaming system over P2P networks so that PVRs can share TV programs with each other. We propose cooperative buffering schemes to provide the streaming services for time-shifted periods even when the number of PVRs playing back at the periods is not sufficient; we do so by utilizing the idle resources of the PVRs playing at the live broadcast time. To determine which chunks to be buffered, they consider the degree of deficiency and proximity and the ratio of playback requests to chunk copies. Through extensive simulations, we show that our proposed buffering schemes can significantly extend the time-shifting hours and compare the performance of two buffering schemes in terms of playback continuity and startup delay.
Sorption of 137Cs and 90Sr on Organic Sorbents
Authors: Belousov Petr , Semenkova Anna , Izosimova Yulia , Tolpeshta Inna , Romanchuk Anna , Zakusin Sergey , Tyupina Ekaterina , Krupskaya Victoria
Published: December 2021

The present study examines the sorption of Cs (I) and Sr (II) on organic sorbents in the pH range from 2 to 10, as well as the mechanisms of their binding. In order to determine the influence of the physical properties and the quantity of functional groups of the organic sorbents on sorption, experiments were carried out on organic materials of varying degrees of metamorphism: high-moor peat, hard and brown coals and shungite. A detailed description of their mineral composition, cation exchange capacity, buffering capacity and elemental composition of sorbents is provided. XRD, XRF, SEM and BET adsorption methods were used for assaying. As a result of the conducted research, it can be concluded that Sr (II) showed a higher sorption per unit specific surface area than Cs (I) in the studied range of concentrations and pH values. Sr (II) sorption decreases in the following order: high-moor peat > brown coal > shungite > hard coal. The sorption of Cs (I) is highest on brown coal and lesser for high-moor peat, shungite and hard coal. It is suggested that Cs (I) and Sr (II) can be fixed on carboxyl functional groups and Cs (I), possibly, in insignificant amounts on phenolic hydroxyls of all four studied organic sorbents.
Inflammatory Biomarkers in Addictive Disorders
Authors: Morcuende Alvaro , Navarrete Francisco , Nieto Elena , Manzanares Jorge , Femenía Teresa
Published: December 2021

Substance use disorders are a group of diseases that are associated with social, professional, and family impairment and that represent a high socio-economic impact on the health systems of countries around the world. These disorders present a very complex diagnosis and treatment regimen due to the lack of suitable biomarkers supporting the correct diagnosis and classification and the difficulty of selecting effective therapies. Over the last few years, several studies have pointed out that these addictive disorders are associated with systemic and central nervous system inflammation, which could play a relevant role in the onset and progression of these diseases. Therefore, identifying different immune system components as biomarkers of such addictive disorders could be a crucial step to promote appropriate diagnosis and treatment. Thus, this work aims to provide an overview of the immune system alterations that may be biomarkers of various addictive disorders.
Emerging Role of Flavonoids as the Treatment of Depression
Authors: Pannu Arzoo , Sharma Prabodh Chander , Thakur Vijay Kumar , Goyal Ramesh K.
Published: December 2021

Depression is one of the most frequently observed psychological disorders, affecting thoughts, feelings, behavior and a sense of well-being in person. As per the WHO, it is projected to be the primitive cause of various other diseases by 2030. Clinically, depression is treated by various types of synthetic medicines that have several limitations such as side-effects, slow-onset action, poor remission and response rates due to complicated pathophysiology involved with depression. Further, clinically, patients cannot be given the treatment unless it affects adversely the job or family. In addition, synthetic drugs are usually single targeted drugs. Unlike synthetic medicaments, there are many plants that have flavonoids and producing action on multiple molecular targets and exhibit anti-depressant action by affecting multiple neuronal transmissions or pathways such as noradrenergic, serotonergic, GABAnergic and dopaminergic; inhibition of monoamine oxidase and tropomyosin receptor kinase B; simultaneous increase in nerve growth and brain-derived neurotrophic factors. Such herbal drugs with flavonoids are likely to be useful in patients with sub-clinical depression. This review is an attempt to analyze pre-clinical studies, structural activity relationship and characteristics of reported isolated flavonoids, which may be considered for clinical trials for the development of therapeutically useful antidepressant.
Butyrate and Metformin Affect Energy Metabolism Independently of the Metabolic Phenotype in the Tumor Therapy Model
Authors: Meyer Felix B. , Marx Christian , Spangel Sonja B. , Thierbach René
Published: December 2021

The BALB/c cell transformation assay (BALB-CTA) considers inter- and intra-tumor heterogeneities and affords the possibility of a direct comparison between untransformed and malignant cells. In the present study, we established monoclonal cell lines that originate from the BALB-CTA and mimic heterogeneous tumor cell populations, in order to investigate phenotype-specific effects of the anti-diabetic drug metformin and the short-chain fatty acid butyrate. Growth inhibitory effects were measured with a ViCell XR cell counter. The BALB/c tumor therapy model (BALB-TTM) was performed, and the extracellular glucose level was measured in the medium supernatant. Using a Seahorse Analyzer, the metabolic phenotypes of four selected clones were characterized, and effects on energy metabolism were investigated. Anti-carcinogenic effects and reduced glucose uptake after butyrate application were observed in the BALB-TTM. Metabolic characterization of the cell clones revealed three different phenotypes. Surprisingly, treatment with metformin or butyrate induced opposite metabolic shifts with similar patterns in all cell clones tested. In conclusion, the BALB-TTM is a relevant model for mechanistic cancer research, and the generation of monoclonal cell lines offers a novel possibility to investigate specific drug effects in a heterogeneous tumor cell population. The results indicate that induced alterations in energy metabolism seem to be independent of the original metabolic phenotype.
RFLMDA: A Novel Reinforcement Learning-Based Computational Model for Human MicroRNA-Disease Association Prediction
Authors: Cui Linqian , Lu You , Sun Jiacheng , Fu Qiming , Xu Xiao , Wu Hongjie , Chen Jianping
Published: December 2021

Numerous studies have confirmed that microRNAs play a crucial role in the research of complex human diseases. Identifying the relationship between miRNAs and diseases is important for improving the treatment of complex diseases. However, traditional biological experiments are not without restrictions. It is an urgent necessity for computational simulation to predict unknown miRNA-disease associations. In this work, we combine Q-learning algorithm of reinforcement learning to propose a RFLMDA model, three submodels CMF, NRLMF, and LapRLS are fused via Q-learning algorithm to obtain the optimal weight S. The performance of RFLMDA was evaluated through five-fold cross-validation and local validation. As a result, the optimal weight is obtained as S (0.1735, 0.2913, 0.5352), and the AUC is 0.9416. By comparing the experiments with other methods, it is proved that RFLMDA model has better performance. For better validate the predictive performance of RFLMDA, we use eight diseases for local verification and carry out case study on three common human diseases. Consequently, all the top 50 miRNAs related to Colorectal Neoplasms and Breast Neoplasms have been confirmed. Among the top 50 miRNAs related to Colon Neoplasms, Gastric Neoplasms, Pancreatic Neoplasms, Kidney Neoplasms, Esophageal Neoplasms, and Lymphoma, we confirm 47, 41, 49, 46, 46 and 48 miRNAs respectively.
Structural Vibration Control with the Implementation of a Tuned Mass Rocking Wall System
Authors: Lin Wei , Wang Andong , Chen Shanghong , Qi Ai , Su Zhonggao
Published: December 2021

A tuned mass rocking wall (TMRW)-frame structure system is proposed to improve the energy dissipation ability of the traditional rocking wall-frame system. Based on the energy dissipation principle of the traditional tuned mass damper (TMD), a TMRW is designed with proper mass and stiffness according to the dynamic characteristic of the host structure. Firstly, considering the presence of inherent structural damping, the dynamic amplification factor of the main mass was derived from the dynamic equations of the TMRW mechanism. A practical design table was then obtained after parameter study. Secondly, by taking a six-story frame structure as an example, the dynamic time-history analysis was conducted to study TMRW’s seismic performance. The inter-story drift ratios of the TMRW-frame, the traditional rocking wall-frame, and the frame structures were compared, and the seismic responses of the controlled and uncontrolled structures were also compared. The results demonstrate that the TMRW can effectively reduce the inter-story displacement of the host structure, and the lateral deformation mode of the host structure tends to be more uniform. However, compared with the traditional rocking wall-frame system, the proposed TMRW has less ability on coordinating deformation.
Direct Interaction of miRNA and circRNA with the Oncosuppressor p53: An Intriguing Perspective in Cancer Research
Authors: Bizzarri Anna Rita , Cannistraro Salvatore
Published: December 2021

MicroRNAs (miRNAs) are linear single-stranded non-coding RNAs oligonucleotides, widely distributed in cells, playing a key role as regulators of gene expression at post-transcriptional level. Circular RNAs (circRNAs) are single-stranded RNA oligonucleotides forming a covalently closed continuous loop, which confers them a high structural stability and which may code for proteins or act as gene regulators. Abnormal levels or dysregulation of miRNA or circRNA are linked to several cancerous pathologies, so that they are receiving a large attention as diagnostic and prognostic tools. Some miRNAs and circRNAs are strongly involved in the regulatory networks of the transcription factor p53, which plays a pivotal role as tumor suppressor. Overexpression of miRNAs and/or circRNAs, as registered in a number of cancers, is associated to a concomitant inhibition of the p53 onco-suppressive function. Among other mechanisms, it was recently suggested that a functional inhibition of p53 could arise from a direct interaction between p53 and oncogenic miRNAs or circRNAs; a mechanism that might be reminiscent of the p53 inhibition by some E3 ubiquitin ligase such as MDM2 and COP1. Such evidence might deserve important implications for restoring the p53 anticancer functionality, and pave the way to intriguing perspectives for novel therapeutic strategies. In the present paper, the experimental evidence of the interaction between p53 and miRNAs and/or circRNAs is reviewed and discussed in connection with the development of new anticancer approaches.
Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas
Authors: Shoji Tadahiro , Tatsuki Shunsuke , Abe Marina , Tomabechi Hidetoshi , Takatori Eriko , Kaido Yoshitaka , Nagasawa Takayuki , Kagabu Masahiro , Baba Tsukasa , Itamochi Hiroaki
Published: December 2021

Ovarian cancer has the worst prognosis among gynecological cancers. In particular, clear cell and mucinous carcinomas are less sensitive to chemotherapy. The establishment of new therapies is necessary to improve the treatment outcomes for these carcinomas. In previous clinical studies, chemotherapy with cytotoxic anticancer drugs has failed to demonstrate better treatment outcomes than paclitaxel + carboplatin therapy. In recent years, attention has been focused on treatment with molecular target drugs and immune checkpoint inhibitors that target newly identified biomarkers. The issues that need to be addressed include the most appropriate combination of therapies, identifying patients who may benefit from each therapy, and how results should be incorporated into the standard of care for ovarian clear cell and mucinous carcinomas. In this article, we have reviewed the most promising therapies for ovarian clear cell and mucinous carcinomas, which are regarded as intractable, with an emphasis on therapies currently being investigated in clinical studies.
Survival Outcome and Prognostic Factors for Pancreatic Acinar Cell Carcinoma: Retrospective Analysis from the German Cancer Registry Group
Authors: Petrova Ekaterina , Wellner Joachim , Nording Anne K. , Braun Rüdiger , Honselmann Kim C. , Bolm Louisa , Hummel Richard , Klinkhammer-Schalke Monika , Zeissig Sylke Ruth , Kleihues van Tol Kees , Timme-Bronsert Sylvia , Bronsert Peter , Zemskov Sergey , Keck Tobias , Wellner Ulrich Friedrich
Published: December 2021

Background: Pancreatic acinar cell carcinoma (PACC) is a distinct type of pancreatic cancer with low prevalence. We aimed to analyze prognostic factors and survival outcome for PACC in comparison to pancreatic ductal adenocarcinoma (PDAC), based on data from the German Cancer Registry Group. Methods: Patients with PACC and PDAC were extracted from pooled data of the German clinical cancer registries (years 2000 to 2019). The distribution of demographic parameters, tumor stage and therapy modes were compared between PACC and PDAC. The Kaplan–Meier method and Cox regression analysis were used to delineate prognostic factors for PACC. Propensity score matching was used to compare survival between PACC and PDAC. Results: There were 233 (0.44%) patients with PACC out of 52,518 patients with pancreatic malignancy. Compared to PDAC, patients with PACC were younger (median age 66 versus 70, respectively, p < 0.001) and the percentage of males was higher (66.1% versus 53.3%, respectively, p < 0.001). More patients were resected with PACC than with PDAC (56.2% versus 38.9%, respectively, p < 0.001). The estimated overall median survival in PACC was 22 months (95% confidence interval 15 to 27), compared to 12 months (95% confidence interval 10 to 13) in the matched PDAC cohort (p < 0.001). Surgical resection was the strongest positive prognostic factor for PACC after adjusting for sex, age, and distant metastases (hazard ratio 0.34, 95% confidence interval 0.22 to 0.51, p < 0.001). There was no survival benefit for adjuvant therapy in PACC. Conclusions: PACC has overall better prognosis than PDAC. Surgical resection is the best therapeutic strategy for PACC and should be advocated even in advanced tumor stages.
Multifaceted Roles of Chemokines and Chemokine Receptors in Tumor Immunity
Authors: Matsuo Kazuhiko , Yoshie Osamu , Nakayama Takashi
Published: December 2021

Various immune cells are involved in host tumor immune responses. In particular, there are many T cell subsets with different roles in tumor immunity. T-helper (Th) 1 cells are involved in cellular immunity and thus play the major role in host anti-tumor immunity by inducing and activating cytotoxic T lymphocytes (CTLs). On the other hand, Th2 cells are involved in humoral immunity and suppressive to Th1 responses. Regulatory T (Treg) cells negatively regulate immune responses and contribute to immune evasion of tumor cells. Th17 cells are involved in inflammatory responses and may play a role in tumor progression. However, recent studies have also shown that Th17 cells are capable of directly inducting CTLs and thus may promote anti-tumor immunity. Besides these T cell subsets, there are many other innate immune cells such as dendritic cells (DCs), natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs) that are involved in host immune responses to cancer. The migratory properties of various immune cells are critical for their functions and largely regulated by the chemokine superfamily. Thus, chemokines and chemokine receptors play vital roles in the orchestration of host immune responses to cancer. In this review, we overview the various immune cells involved in host responses to cancer and their migratory properties regulated by the chemokine superfamily. Understanding the roles of chemokines and chemokine receptors in host immune responses to cancer may provide new therapeutic opportunities for cancer immunotherapy.
Opportunity for GNSS Reflectometry in Sensing the Regional Climate and Soil Moisture Instabilities in Myanmar
Authors: Lwin Aung , Yang Dongkai , Hong Xuebao , Zhang Bo , Zhang Baoyin , Sara Cheraghi Shamsabadi
Published: December 2021

The climate crisis is happening globally, and the consequent process has revealed soil evolution and meteorological interactions. The GNSS reflectometry (GNSS-R) technique recently encompassed sea surface monitoring, land changes, and snow sensing in addition to position, navigation, and timing. After the launch of NASA’s eight CYGNSS satellites, spaceborne soil moisture retrieval has become more opportune in a global and regional investigation. The research carried out by the CYGNSS DDM SNR with SMAP data to correlate diurnal mean soil moisture sensing was analyzed in the regional study of Myanmar, which is prone to climatic and weather conditions. The results showed that spaceborne GNSS-R soil moisture sensitivity was very useful during seasonal changes in regional observation. The DDM SNR surface reflectivity was strongly correlated with soil moisture according to surface temperature variations prepared from SMAP passive reflectometry. Sentinel SAR-1 data included the validation and verification of flood-prone areas affected by tropical storm surges or weather depressions in the monsoon season. The availability of surface reflectivity primarily relied on the surface roughness, surface temperature, and vegetation opacity for soil moisture retrieval.
Diversity of Ruderal Communities in Urban Environments—A Case Study from Serbia (SE Europe)
Authors: Tabašević Milena , Jovanović Slobodan , Lakušić Dmitar , Vukojičić Snežana , Kuzmanović Nevena
Published: December 2021

The high diversity of ruderal vegetation in urban environments is well known. Although it has been a subject of numerous studies in Serbia, in recent years it has been slightly overlooked, although, due to the dynamics of ruderal habitats, constant research is required. We investigated ruderal vegetation in 20 cities across Serbia during a period of 5 years. Most of the relevés were collected during the summer months, and within 712 relevés, 422 taxa were recorded. Results of the cluster analyses and identified diagnostic species revealed 26 plant communities, of which nine are dominated or co-dominated by aliens. The relevés can be grouped into six ecologically well-differentiated major vegetation groups. Our study revealed the ruderal communities which are the most widespread in urban environments in Serbia. Additionally, some communities were registered for the first time in the country.