bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant MEK5 Signalling Promotes Renal Cancer Development via mTOR Activation
Authors: Li Fangzhou , Peng Xu Feng , Zhou Jiale , Chen Qi , Chen Yonghui 
Published: November 2021

Abstract
Purpose: Renal cell carcinoma is one of the most incident malignancies globally. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. However, comprehensive clinical treatment has some limitations. Therefore, exploring the pathogenesis and identifying novel therapeutic targets are required urgently. MEK5 has been reported to play an essential role in the development of various cancers. However, no study has evaluated its role and specific mechanisms in ccRCC. Methods: Using the ONCOMINE database, MEK5 expression in ccRCC and normal tissues was compared. ccRCC and adjacent normal tissues were collected from fourteen ccRCC patients, and ccRCC expression was assessed by qPCR and immunohistochemistry. MEK5 overexpression and knockdown plasmids were constructed and transfected into ccRCC cells. CCK8, wound-healing assay, and clone formation assay were performed to examine the cell proliferation, migration, and clone formation ability of ccRCC cells. Furthermore, a western blot was performed to verify the regulation and influence of MEK5 on the mTOR signaling pathway. The MEK5 small molecule inhibitor BIX was used to treat cells, followed by CCK8, wound-healing assay, clone formation, and flow cytometry assay to examine the cell proliferation, migration, clone formation ability, apoptosis, and cell cycle. Finally, a murine subcutaneous tumor model was constructed, and the effect and safety of BIX were evaluated in-vivo.Results: The ONCOMINE database indicated that the MEK5 expression in ccRCC was significantly higher than the normal tissues, further confirmed in clinical specimens. The knockdown of MEK5 markedly inhibited the ability of ccRCC cell proliferation, colony formation, and migration. In contrast, MEK5 overexpression promoted cell proliferation, colony formation, and migration. Western blotting showed that overexpression of MEK5 can further activate the mTOR signaling pathway. The MEK5 inhibitor, BIX treatment of ccRCC, significantly inhibited cell proliferation, arrested the cell cycle in the G0/G1 phase, induced apoptosis, and effectively inhibited cell migration and clone formation. BIX also showed an excellent anti-tumor effect and favorable safety profile in murine models.Conclusions: MEK5 regulated the mTOR signal pathway and regulated the cell proliferation, cycle, migration, clone formation of ccRCC. Targeted inhibition of MEK5 had a good anti-tumor effect and favorable safety profile, providing new directions for ccRCC therapy.
Awareness, Perceived Efficacy, and Utilization of Assisted Reproductive Technologies Among Women Attending Infertility Clinic in a Nigerian Tertiary Health Institution: A Cross-Sectional Study
Authors: Chikeme Paulina Chigwara , Arinze Bekuochi Lilian 
Published: November 2021

Abstract
BackgroundInfertility is a source of distress for couples considering the high accolade placed on having children in family settings in Nigeria. Assisted reproductive technologies (ARTs) offer a chance of parenthood to couples. However, studies on knowledge of ART abound in Nigeria but no previous studies exist on the extent of utilization of assisted reproductive technologies. This study thus explored the level of awareness, perceived efficacy and utilization of ARTs among women attending infertility Clinic in a Nigerian Tertiary Health Institution.Methods This cross-sectional study which utilized a self-administered questionnaire was adopted for this study. The questionnaire contains five sections with section A to E bordering on demographics, awareness, perceived efficacy, utilization, and factors influencing utilization respectivelyResultsOne hundred and seven women with infertility problems, aged between 26-35 years with a mean age of 31.46 ± 5.72 participated in the study. Sixty-two patients (57.9%) were aware of ARTs while 97 (90.7%) believed that ART cannot address male infertility. Only 27 (25.2%) admitted to have used ART procedures before while 82 patients (76.6%) stated that cost of the procedure was the major hindrance to use. Conclusions Awareness of ARTs is average while there is low utilization and perceived efficacy of ART. High cost of the procedure remains the major setback to its utilization
Structural Analysis of Traditional Chinese Complex Puzzle Locks
Authors: Shi Kan , Wang Ming-Jie , Zhang Yang , Hsiao Kuo-Hung , Yao Yan-An 
Published: November 2021

Abstract
The development of barbed-spring locks in ancient China has a history of more than two thousand years. With the development of the design and manufacturing techniques in ancient China, the safety of locks has gotten better and better. Since the 17th century, the puzzle lock, with a complicated structure and a high difficulty in opening, was gradually developed and used. The puzzle lock needs specific steps to be opened. Even if strangers have the correct key, it is still difficult for them to open the lock immediately. Based on the difficulty of the opening process, traditional Chinese puzzle locks can be partition into two sorts, namely, general puzzle locks and complex puzzle locks. As the structure of the puzzle lock will change during the opening process, the puzzle lock belongs to the reconfigurable mechanism. In this paper, a method of topology matrix is provided to analyze the structure of the complex puzzle lock during operation systematically. Firstly, the characteristics and types of general puzzle locks are explained, and then the topology matrix representation is introduced. Finally, four complex puzzle locks are taken as examples, to illustrate the opening process. There are various types of complex puzzle locks, and the mechanism designs are quite ingenious and interesting, which shows the extraordinary technique and ingenuity of the ancient craftsmen.
Genistein Mitigates High Glucose-Induced Podocyte Adhesion Injury by Modulating Autophagy via Mtor Signal
Authors: Lian Yuhang , Tian Zhixia , Cao Haiyan , Jia Zhonghui , Yan Tiekun , Li Dong 
Published: November 2021

Abstract
Purpose: The study aimed to investigate the characteristics of autophagy on podocyte under high glucose (HG) conditions and further explore the effect of Genistein on podocyte autophagy，adhesion and the potential mechanism.Materials and methods: CCK-8 was used to detect the viability of podocyte. The level of autophagy was mainly detected by western blot and immunofluorescence. The expression of autophagy related factors and podocyte adhesion markers, including LC3-II, p62, p-mTOR and integrin β1-MF, were detected by immunofluorescence at 0，6，12，24，36，48，72h. The expression levels of proteins in the LC3-II, p62, p-mTOR/mTOR, integrin β1-MF were further investigated by western blot. Wound healing test and cell migration assay were used to detect podocyte adhesion ability.Results: The present study showed that HG-induced podocyte viability was reduced significantly for 6 h. Decreased integrin β1-MF, LC3-II, increased p62 and abnormal activation of the mTOR signal was detected in podocyte under HG conditions. Genistein restored podocyte viability and up-regulated integrin β1-MF, LC3-II expression, down-regulated p62, p-mTOR expression. Moreover, the HG-induced podocyte adhesion injury was abrogated by treatment with Genistein.Conclusion：Our results demonstrated that podocyte adhesion injury in HG environment was related to the decrease of autophagy level. Genistein activated podocyte autophagy by inhibiting the mTOR signaling pathway, regulated the renewal expression of integrin β1-MF, and finally reduced HG-induced podocyte adhesion injury.
Improvement in Sintered Tungsten Carbide Tool Surface Integrity Using Femtosecond Pulse Laser
Authors: Konda Osamu , Liu Xiaoxu , Maegawa Satoru , Itoigawa Fumihiro 
Published: November 2021

Abstract
In this paper, we propose a surface integrity technique referred to as pulse laser grinding (PLG). This method is a combination of laser ablation and averaging processes, such as grinding, and has two characteristic features. The first feature is that the irradiation area consists of a long-focus lens and a pulse laser with a Gaussian profile, and this method has a laser irradiation area equivalent to that of the grinding wheel. However, owing to the difference in the removal process of PLG and that of conventional grinding, the surface roughness after processing is expected to be different. The second feature is that the workpiece is placed at an approximately parallel angle between the laser axis and the work surface to undergo laser ablation on the surface. The characteristic piece placement restrains laser-specific problems such as debris and redeposition. This study targets sintered tungsten carbide (WC-Co), for which it is particularly difficult to form low-roughness surfaces. Binder removal followed by WC grain detachment caused by conventional grinding contributes to the increase in roughness and deterioration of corner sharpness. The experimental results of PLG with a sufficiently averaged surface of a WC-Co tool confirmed that the parallel roughness reached an arithmetical mean roughness (Ra) of 0.025 μm, and the perpendicular roughness reached Ra below 0.006 μm, in agreement with the aforementioned considerations.
Optimal Positive End-Expiratory Pressure Obtained with Titration of Fraction of Inspiratory Oxygen: A Randomized Controlled Clinical Trial
Authors: Gao Lingling , Yang Li , Pan Lili , Cui Yun , Jiang Yandong , Zhang Jun 
Published: November 2021

Abstract
Background
Optimal intraoperative positive end expiratory pressure (PEEP) improves patient outcomes. The pulse-oximetry has been used to determine the lung opening and closing pressures. Therefore, we hypothesized that intraoperative optimal PEEP obtained by titrating inspiratory oxygen fraction (FiO2) guided with pulse-oximetry could improve perioperative oxygenation.
Methods
Forty-six males undergoing elective robotic assisted laparoscopic prostatectomy were randomly assigned to either optimal PEEP (Group O, n=23) or control with fixed PEEP of 5 cmH2O (Group C, n=23). Optimal PEEP, defined as the PEEP with lowest FiO2 or 0.21 to maintain SpO2≥ 95%, was obtained in both groups after placing the patients in Trendelenburg position and peritoneal insufflation. Patients in Group O maintained the optimal PEEP and in Group C maintained PEEP of 5cmH2O intraoperatively. Both groups were extubated in a sitting position once the extubation criteria met. The primary outcome was the partial arterial oxygen pressure (PaO2)/inspiratory oxygen fraction (FiO2) prior to extubation. Secondary outcome was the incidence of postoperative hypoxemia (SpO2༜92% on room-air after extubation) in post-operative care unit.
Results
The median optimal PEEP was 16 cm H2O [inter-quartile range, 12-18]. The PaO2/FiO2prior to extubation was significantly higher in Group O than that in Group C (77.0±4.9kPa vs.60.6±5.9kPa, p=0.04); PaO2/FiO2 was also significantly higher in Group O 30minutes after extubation (57.6±1.9 vs. 46.6±1.8kPa, p=0.01). The incidence of hypoxemia on room air in the post-operative care unit was significantly lower in the Group O than in the Group C (1/23, or 4.3% vs. 7/23 or 30.4%, p =0.02).
Conclusions
Intraoperative optimal PEEP can be achieved by titration of FiO2 guided with SpO2. Maintaining intraoperative optimal PEEP improves intraoperative oxygenation and reduces the incidence of post-operative hypoxemia.
Trial registration
: Chinese Clinical Trial Registry identifier: ChiCTR2100051010. Prospectively registered on 10 September, 2021
Association Between Thyroid Cancer and Cardiovascular Disease Risk: A Nationwide Observation Study
Authors: Tsai Ming-Chieh , Hsieh Cheng-Tzu , Hsu Hsin-Yin , Yeh Tzu-Lin , Lee Wen-Chung , Chiang Chun-Ju , Hsiao Bo-Yu , Jhuang Jing-Rong , Tsai Wen-Hsuan , Cheng Shih-Ping , Chou Chao-Liang , Lee Chun-Chuan , Liu Sung-Chen , Tseng Po-Jung , Chien Kuo-Liong 
Published: November 2021

Abstract
BackgroundResearch findings on the long-term cardiovascular risk associated with thyroid cancer and treatment are unclear. This study aimed to investigate the standardized incidence rate (SIR) of coronary heart disease (CHD), ischemic stroke (IS), and atrial fibrillation (AF) among thyroid cancer patients in comparison with the general population across different age groups. MethodsDesign, setting, and participantsThis observational cohort study enrolled patients between January 1, 2011 and December 31, 2016 with follow-up until December 31, 2018. This study analyzed the data of Taiwanese thyroid cancer patients registered on the National Taiwan Cancer Registry Database, with CHD and IS. Main outcomes and measuresSIR models were used to evaluate the association between thyroid cancer and CHD, IS, AF, and cardiovascular disease outcome, stratified by age and sex. SIR analyses were also conducted for both sexes, age groups (<60, ≥60 years), and different follow-up years.ResultsAfter excluding 128 individuals <20 years or >85 years and with missing index data, 4274 eligible thyroid cancer patients without CHD history, 4343 patients without IS history, and 4247 patients without AF history were included for analysis. During the median follow-up of 3.5 (1.2) years, CHD incidence was 70; IS, 30; and AF, 20. Compared with the general population, thyroid cancer patients had higher CHD risk throughout the age spectrum (SIR, 1.33; 95% confidence interval [CI], 1.02 to 1.65). The overall CHD risk gradually declined, but it was persistent for more than 5 years after thyroid cancer diagnosis. CHD risk was observed in both males and females, especially in young thyroid cancer patients <65 years. However, lower SIRs for IS (SIR, 0.74; 95% CI, 0.47 to 1), AF (SIR, 0.74; 95% CI, 0.42 to 1.06), and cardiovascular disease (SIR, 0.88; 95% CI, 0.7 to 1.05) were observed among thyroid cancer patients (not significant). ConclusionsThyroid cancer survivors have a substantial CHD risk even at long-term follow-up, especially in those patients <65 years. Further research on the association between thyroid cancer and CHD risk is warranted.
Effect of Combination Treatments of Apigenin and Chemotherapy on Apoptosis- Related Genes and Proteins in Acute Leukaemia Cell Lines
Authors: Mahbub Amani A. , Maitre Christine L. Le , Cross Neil A. , Jordan-Mahy Nicola 
Published: November 2021

Abstract
Apigenin is a dietary polyphenol found abundantly in fruit and vegetables. It has been shown to sensitize acute lymphoid and myeloid leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and alkylating agents (e.g., cyclophosphamide), reducing ATP levels and inducing apoptosis; whilst being protective to control haematopoietic stem cells. This study analysed the expression profiles of intrinsic and extrinsic apoptosis-related genes and proteins to help elucidate the mechanisms of action of apigenin when used in combination with etoposide or cyclophosphamide in acute lymphoid and myeloid leukaemia cells (Jurkat and THP-1). Expression of apoptosis-related genes were measured using a TaqMan® Human Apoptosis Array and the StepOne Plus RT-qPCR System, whilst apoptosis-related proteins were determined using a protein profilerTM-human apoptosis array and the LI-COR OdysseyR Infrared Imaging System. Apigenin when combined with etoposide or cyclophosphamide-induced apoptosis via the mitochondrial pathway, increasing the expression of pro-apoptotic cytochrome c, SMAC/DIABLO, and HTRA2/OMI, which promoted caspase-9 and -3 activation. Targeting anti-apoptotic and/or pro-apoptotic members of the apoptotic pathways is a promising strategy to induce cancer cell death and improve sensitivity to chemotherapy agents.Here apigenin in combination with etoposide or cyclophosphamide induced apoptosis in leukaemia cells and may have clinical potential in the treatment of leukaemia.
Toward the Creation of Disaster-Resilient Communities: The Machizukuri Initiative – the 2011 Tōhoku Great East Japan Earthquake and Tsunami
Authors: Siawsh Nidam Marcus , Peszynski Konrad , Vo-Tran Huan , Young Leslie 
Published: November 2021

Abstract
Community engagement and involvement is an essential component of managing and responding to disasters. In Japan, greater community involvement and increased participation of its citizens has been encouraged through the machizukuri initiative. The machizukuri are local community councils that played a pivotal role in the recovery efforts following the Tōhoku Great East Japan Earthquake and Tsunami (GETET) that devastated much of northern Japan in 2011. However, their role in those efforts is not well understood.Thus, the aim of this study was to better understand the role and impact of local communities in responding to and recovering from disasters through examining the role of the machizukuri following the GEJET. An exploratory approach was adopted, and semi-structured interviews were undertaken with eight key decision-makers involved in recovery efforts. Key themes were identified including the overwhelming nature of the GEJET for which Japan was unprepared, and while the central government enacted their disaster management plans, responses were slow and failed to address local priorities. To compensate, the local community and machizukuri assisted and successfully united the local community to fill a gap left by the centralized governments’ approach. It is an example of an effective bottom-up approach to address a critical issue. However, the efforts were hindered by a lack of coordination between the various government bodies and aid organisations as well as communication failures that prevented a more coherent response. Recommendations were made to assist countries to remediate these shortcomings and respond more effectively to disasters.
Exosome-delivered miR-15a/16 Targets PD-L1 to Inhibit Immune Escape in Gastric Cancer
Authors: Yang Changliang , Zhang Qiumo , Zuo Mengsi , Yang Jiayu , Ning Tao , Deng Ting , Liu Rui , Bai Ming , Zhang Haiyang , Ying Guoguang , Ba Yi 
Published: November 2021

Abstract
Recently, immunotherapy targeting immune checkpoints, especially PD-1/PD-L1 blockade, has been demonstrated to play a crucial role in numerous malignancies to rejuvenate disabled T cells to achieve long-term remission. However, the underlying mechanism of PD-L1 expression dysregulation in gastric cancer (GC) has not been revealed. The present study aimed to determine whether artificially modified exosomes transporting miR-15a/16 target PD-L1 and inhibit immune escape in GC. Modified exosomes serve as novel nanoliposomes to suppress tumor growth and inhibit immune escape by targeting PD-L1 in vivo and in vitro. The present study also suggested that the combination of exosomal miR-15a/16 can be used in immunotherapy against tumors, including gastric cancer.
Parasagittal Dural Space and Cerebrospinal Fluid (CSF) Changes Across the Lifespan in Healthy Adults: Implications for Glymphatic Flow
Authors: HETT Kilian , Mcknight Colin D. , Eisma Jarrod J. , Elenberger Jason , Lindsey Jennifer D. , Considine Ciaran M. , Claassen Daniel O. , Donahue Manus J. 
Published: November 2021

Abstract
Background: Recent studies have suggested the importance of a glymphatic clearance pathway for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of this pathway is the anatomic region surrounding the superior sagittal sinus, which has been hypothesized to encompass lymphatic vessels. This so-called parasagittal dural (PSD) space likely plays a physiologically significant role at the distal intracranial component of the human glymphatic circuit, yet owing to the relative novelty of this discovery, fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport. Methods: We tested the hypotheses that volumetric magnetic resonance imaging (MRI) measures of the PSD space (i) are directly related to cerebrospinal fluid (CSF) flow at the cerebral aqueduct, and (ii) increase with age. Healthy participants (n=62; age range = 20-83 years) provided informed, written consent and multi-modal 3 Tesla MRI was performed including phase contrast assessment of the CSF flow through the aqueduct of Sylvius, T1-weighted and T2-weighted MRI for tissue volume and PSD assessment. Standard anatomical and cognitive testing were applied to confirm inclusion criteria. PSD volume was extracted using a recently validated neural networks algorithm. Non-parametric regression models were applied to evaluate how PSD volume related to tissue volume and age cross-sectionally, and separately how PSD volume related to CSF flux (significance criteria: two-sided p<0.05). Results: A significant enlargement of PSD volume in relation to normal aging (p<0.001, Spearman’s- =0.6), CSF volume (p<0.001, Spearman’s- =0.6) and bulk CSF flux through the aqueduct of Sylvius (anterograde and retrograde, p<0.001) were observed. The elevation in PSD volume was not significantly related to changes in tissue volume (p=0.11 and p=0.24 for gray and white matter, respectively). Findings are consistent with PSD volume increasing with age and bulk CSF flux.Conclusions: The findings of this study are two folds, first they highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Second, that PSD volume increases with age, and relates to bulk CSF volume and flux. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders.
Effect of Zinc Dialkyl Dithiophosphate Replenishment on Tribological Performance of Heavy-Duty Diesel Engine Oil
Authors: Omar Alaaeddin Al Sheikh , Salehi F. Motamen , Farooq U. , Neville A. , Morina A. 
Published: November 2021

Abstract
Soot is the main contamination that affects oil performance and increases oil drain intervals in heavyduty engine oil. It is also believed that additive concentration in engine oil can be influenced due to additive depletion over time and additive adsorption on soot particles. To extend oil drain intervals and improve oil performance, filter manufactures explore removing the soot to a certain level and replenishing the consumed additives. Zinc Dialkyl Dithiophosphate (ZDDP) is one of the most favoured anti-wear additives that reacts very rapidly with rubbing surfaces to form tribofilm that reduce wear. In this study, the experimental work aims to investigate the effect of ZDDP replenishment on tribological performance in the existence of soot and after removing soot from heavy-duty used oil. The study reveals that reclaiming the used oil can be achieved by removing the soot to a certain level. The results demonstrate that the reclaimed oil after removing soot is still not as good as the fresh oil. This study proves that additive depletion, additive adsorption on soot and the decomposition of antiwear additive adversely influence the reclaimed oil performance. However, replenishing the consumed additive by adding a small amount of ZDDP helps to improve the reclaimed oil performance compared to a large amount of ZDDP which is required to re-gain the oil performance in the existence of soot.