bluuebunny/crossref_metadata_2025 huggingface dataset:
Testicular Histone Hyperacetylation in Mice by Valproic Acid Administration Affects the Next Generation by Changes in Sperm DNA Methylation
Authors: Sakai Kazuya , Hara Kenshiro , Tanemura Kentaro
Published: May 2022

Various reports have described epigenetic transgenerational inheritance through sperm. However, the detailed mechanism remains unclear. In this study, we focused on DNA methylation and analyzed the effects on the next generation of sperm from mice treated with valproic acid (VPA) as an inducer of epigenomic changes. Administration of 200 mg/kg/day VPA to mice for 4 weeks caused transient histone hyperacetylation in the testes and DNA methylation changes in sperm, including promoter CpGs of genes related to brain function. Oocytes fertilized by VPA-treated mouse sperm showed some methylation fluctuations at the morula stage. Pups fathered by these mice also showed behavioral changes in the light/dark transition test after maturation. Brain RNA-seq of these mice showed decreased expression of many genes related to brain and neural function. Comparison of the sperm DNA methylation status of the next generation of mice with that of the parental generation revealed the disappearance of the methylation changes observed in the sperm of the parental generation. These findings suggest that VPA-treated mice may be a useful simple epigenetic transgenerational inheritance model for histone hyperacetylation.
Regionalized Compensation Method for Nonlinear Error Control
Authors: Wei Wei , Tang Qingchun , Wang Yutao , Wang Taizi , Zhang Chenyang , Pan Yingguang
Published: May 2022

Although the five-axis machine tool presents excellent advantages of high-speed, -efficiency, and -precision machining of complex curved surface parts (impeller and blade), its actual motion demonstrates nonlinear principle error due to the participation of the rotating axis. Traditional methods, such as linear interpolation, Rotation Tool Centre Point(RTCP), and tool point optimization, can effectively control nonlinear errors despite their limitations. A regional compensation optimization method is proposed in this study to solve nonlinear error problems effectively in five-axis machining of complex curved surface parts. First, feature points of the complex free-form surface are identified, and regions are divided to distinguish the compensation optimization algorithm of each interval. Second, JAVA language is applied to develop a special postprocessor with nonlinear error partition compensation module. Finally, the BV100 machine tool is used as the experimental platform, and a turbine blade is utilized as the specimen for simulation and cutting experiments. Results showed that the surface quality and contour accuracy of machined parts improved when the nonlinear error regional compensation optimization algorithm is used.
Design, synthesis, antimicrobial evaluation, and in-silico studies of some 4-thiazolidinone hybrids bearing coumarin and pyridine moiety
Authors: Desai Nisheeth C , Mehta Harsh K , Jethawa Aratiba M , Monapara Jahnvi D , Khedkar Vijay M , Dave Bharti P
Published: May 2022

Antimicrobial resistance (AMR) is a major threat to mankind. Many frontline medications are ineffective against antimicrobial-resistant strains which are also responsible for the high mortality rate worldwide. The emergence to create new sets of antimicrobial agents is a priority in present circumstances. In continuation to this, we have strategically designed and synthesized some novel hybrids of 4-thiazolidinone bearing coumarin and pyridine cores for the evaluation of antimicrobial efficacy against microbial pathogens. A three-step multicomponent reaction was performed via imine formation, cyclization, and Michael condensation for the synthesis of titled compounds (5a-o). The synthesized compounds were characterized by various analytical techniques i.e., IR, 1H NMR, 13C NMR, and mass spectra. On evaluating the potency of our synthesized hybrids, we received some promising results. Compound 5m was found to be the most active with a MIC value of 50 µg/mL against S. aureus and 250 µg/mL against C. albicans strains. Further, a molecular docking study against microbial DNA gyrase was carried out to understand the binding profile of synthesized molecules, support their in-vitro antimicrobial activity and gain an insight into their plausible mechanism of action. Their binding affinity scores correlated well with the in-vitro antimicrobial activities while their binding modes proposed the involvement of steric, electrostatic, and hydrogen bonding interactions with the active site.
Proteomic Analysis Reveals sympathetic system and immune-inflammation biomarkers in serum of drug-free obsessive-compulsive disorder
Authors: Xiao Zeping , Wang Yuan , Deng Miaohan , Zhang Haiyin , Fan Qing
Published: May 2022

Obsessive-compulsive disorder (OCD) is a debilitating mental disorder, of which the mechanism is unclear. Biomarker detection will help in the mechanism exploration, early diagnosis and targeted treatment. Therefore, we conducted an iTRAQ-based proteomic analysis to compare serum proteome profile between OCD patients and healthy control, in order to find out the possible biomarkers of OCD and their underlying mechanisms. 81 drug-free OCD patients and 78 healthy controls were enrolled. A total of 479 proteins were identified and only those with a fold change ≥ 1.2 and p value༜0.05 were accepted as differentially expressed proteins (DEPs). 7 up-regulated proteins, and 28 down-regulated ones were discovered. Besides dopamine beta-hydroxylase that plays a part in sympathetic system, lots of other DEPs are involved in immuno-inflammatory process. These DEPs were enriched in 44 gene ontology (GO) terms. However, none of KEGG pathway was detected significantly enriched. Our study suggested these sympathetic system and immuno-inflammation related proteins as potential biomarkers of OCD. Especially, immuno-inflammation may play an important role in OCD pathophysiology. Further researches employing larger sample sizes, longitudinal design and multi-omics methodology will be needed to verify our results and clarify the role of DEPs in OCD.
Smoking cessation in pregnant women using financial incentives: a feasibility study.
Authors: Kroder T. A. , Peters L. L. , Roggeveld A. , Holtrop M. , Harshagen L. , Klein L. M. , Erwich J. J.H.M.
Published: May 2022

Background The high prevalence of smoking pregnant women in Dutch areas with lower socioeconomic status and the consecutively harmful exposure to tobacco to both mother and child, depicted a high need for a novel intervention. According to other studies, the utilisation of financial incentives appeared to be a promising method for smoking cessation in pregnant women. Therefore, the aim of this study was to investigate the feasibility of implementing contingent financial incentives as smoking cessation support for pregnant women in the Netherlands.Methods Feasibility study consisting of four developmental phases: (1) acceptability of Dutch population regarding financial-incentive-intervention by conducting an online questionnaire, (2) composing a pilot study utilising the financial-incentive-intervention in clinical practice, (3) execution of the composed pilot study and (4) evaluation of the executed pilot study utilising a mixed-methods approach. A financial-incentive-intervention, given in a contingent financial scheme (during five consequential appointments, respectively €25/€50/€100/€150/€250), if smoking abstinence was proven by the amount of cotinine in the urine of the pregnant women measured utilising a urine dipstick test.The public acceptability for the financial-incentive-intervention was assessed using 5-Likert scales. The number of pregnant women able to abstain from smoking during the pilot study and utilising the financial-incentive-intervention in clinical practice were used to assess the prosperity and practicality of the pilot study respectively. The pilot study was evaluated using a mixed-methods approach. Results In total, 55.1% of the Dutch population sample (n=328) found a financial incentive inappropriate for smoking cessation in pregnant women, while the healthcare professionals and pilot study participants thought the financial-incentive-intervention to be a helpful approach. Eleven vouchers were given during the pilot study, and one woman completed all test points and tested negative for cotinine at the end of the pilot study.Conclusion Although the financial-incentive-intervention appeared to be a promising approach for smoking cessation in pregnant women, the acceptability of the Dutch population and the number of pregnant women able to abstain smoking during this pilot study was low. Despite the limited study population, this study proved the concept of this financial-incentive-intervention to be feasible for implementation in the Netherlands. Trial registration: Not applicable since this is a feasibility study prior to a trial.
The endometrial preparation protocol of gonadotropin-releasing hormone agonist with hormone replacement therapy can improve the reproductive outcomes in women under FET cycles: a retrospective study.
Authors: Yu Juanjuan , Xiao Qimeng , Lv Mu , Chen Juan , Chen Peiqin , Lou Liqun , Luo Yifan , Hu Meiyan , chen Xiong , Zhang Zhenbo , Bai Mingzhu , Li Linxia
Published: May 2022

Background: Hormone replacement therapy (HRT) is the most commonly used method for the endometrial preparation before frozen embryo transfer (FET), but whether pretreatment with gonadotropin-releasing hormone agonist (GnRH-a) could improve live birth rates remains controversial. This study aims at examining the efficacy of GnRH-a with HRT in the preparation of the endometrium during FET cycles.Methods: The retrospective cohort research of clinical files between January 2016 and October 2020. A total of 6,034 infertile women received HRT as endometrial preparation during the FET cycle at two Reproductive Medicine Centers. Based on whether or not GnRH-a was pretreatment, the study was divided into two groups: HRT cycles consisted of 2404 cycles as the HRT group, and HRT with GnRH-a cycle consisted of 2402 cycles as the GnRHa-HRT group. The primary outcome measure was the live birth rate. Secondary endpoints included the rate of implantation, biochemical pregnancy, clinical pregnancy, miscarriage, biochemical abortion, ectopic pregnancy, multiple pregnancy, preterm delivery, term delivery, low birth weight infant and fetal macrosomia as well as birth weight.Result(s): Among 4,806 participants, baseline characteristics were similar between the two groups. Compared with the HRT group, HRT pretreatment with GnRH-a significantly increased pregnancy outcomes of FET, such as live birth rates (44.5% VS. 38.1%; P=0.000, OR 1.30,95%CI 1.16-1.46), implantation rate (37.9%VS. 33.0%; P=0.000; OR 1.24,95%CI 1.13-1.35). And the GnRHa-HRT group and the HRT group had similar rates of pregnancy loss (25.1% VS. 27.8%; P=0.107, OR 0.87,95%CI 0.74-1.03). GnRHa pretreated with HRT resulted in an increased risk of fetal macrosomia (20.9% VS. 17.3%; P=0.025, OR 1.264,95%CI 1.03-1.55). The other pregnancy complications such as ectopic pregnancy, multiple pregnancies and preterm delivery were no statistical significance between the two protocols.Conclusion(s): Pretreatment with GnRH-a can improve the reproductive outcomes and may increase the risk of pregnancy with macrocephaly, in women receiving HRT in endometrial preparation under FET cycles.
AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin II dependent cell migration
Authors: Sanz-Moreno Victoria , Crosas-Molist Eva Crosas-Molist , Maiques Oscar , Graziani Vittoria , Pandya Pahini , Monger Jo , Samain REmi , George Samantha , Malik Saba , Salise Jerrine , Le_guennec Adrien , Atkinson Robert , Conte Maria , Holt Mark , Charras Guillaume
Published: May 2022

Cell migration are crucial for development, immunity and cancer dissemination. We find that AMPK controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional (3D) matrices, fast migrating amoeboid cancer cells exert low adhesion/low traction linked to lower energy levels; while their low ATP/AMP ratio leads to AMPK activation. In turn, AMPK plays a dual role controlling both mitochondrial dynamics and cytoskeletal remodelling. High AMPK in low adhering migratory cells, induces mitochondrial fission via MFF phosphorylation, resulting in lower OXPHOS and lower mitochondrial ATP. At the same time, AMPK phosphorylates and inactivates MYPT1, increasing Myosin II dependent amoeboid migration. Reducing adhesion, inducing AMPK activity or inhibiting mitochondrial fusion result in profound cytoskeletal remodelling and efficient rounded-amoeboid 3D migration and invasion. Moreover, AMPK inhibition suppresses in vivo metastatic potential of amoeboid cancer cells. We measure a mitochondrial/AMPK-driven switch in regions of human tumours where amoeboid cells are actively disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a master “mechano-metabolic sensor” at the crossroads between energetics and the actomyosin cytoskeleton.
Numerical study of strong shear nonequilibrium phenomenon and its relaxation mechanism in hypersonic Knudsen layer flows based on the direct simulation Monte Carlo method
Authors: wenbin Liu , Liu Wenbin , Jinbai Zhang , Chun-Hian Lee
Published: May 2022

Based on the different flowfield and wall settings, a series of plane Couette flows of rarefied argon gas are simulated by the direct simulation Monte Carlo method, and the relaxation process of shear nonequilibrium has been systematically analyzed. The statistical result of molecular streamwise velocity (vx) shows a qualitatively platform-shaped distribution under the conditions of diffuse-reflection wall, low wall temperature, small wall spacing (roughly within the range of Knudsen layer), and large wall speed and shear rate. The simplified mechanism of this platform-like phenomenon is deduced, which proves that after the collision between two molecules reflected from the different walls (named the dual-wall molecular collision), their vx will be uniformly distributed. Thus, if all reflected molecules occur once dual-wall molecular collision on average, their vx will form the platform-shaped distribution. This conclusion is demonstrated by the verification cases. Similar phenomena can be found in more general flows, such as the hypersonic flow over a flat plate. The nonequilibrium phenomenon in the flat-plate flow can be explained by the equivalent relaxation process of dual-wall molecular collision, which indicates that the platform-like phenomenon is a universal nonequilibrium state in strong-shear rarefied flow, and they share a similar relaxation mechanism. The analysis of this phenomenon will help us to understand and model the relaxation process of hypersonic Knudsen layer flow.
Positron annihilation lifetime spectroscopy of adipose, hepatic, and muscle tissues
Authors: Avachat Ashish V. , Leja Anthony G , Mahmoud Kholod H. , Anastasio Mark A. , Sivaguru Mayandi , Fulvio Angela Di
Published: May 2022

Can positron annihilation lifetime spectroscopy (PALS) be employed to discriminate different types of soft tissues? This work reports our experimental measurements of the three components of positron annihilation lifetime spectra for three types of bovine, non-fixated soft tissues: adipose, hepatic, and muscle. These three components of PALS spectra correspond to contributions from annihilation lifetimes of para-positronium (p-Ps), positron, and ortho-positronium (o-Ps). We also report a benchmark comparison between PALS and X-ray phase-contrast imaging, which is the current state-of-the-art for soft tissue imaging and analysis. Our measurements showed that the joint probability of annihilation from p-Ps and positron in the soft tissues increases with electron density of the tissue and hence correlates well with the mean voxel values measured by X-ray phase-contrast computed tomography. Notably, the o-Ps lifetime in adipose tissue (2.53±0.01 ns) was approximately 25% longer than in hepatic (2.03±0.02 ns) and muscle tissues (2.00±0.01 ns). The significance here is that the o-Ps lifetime is a viable non-invasive probe for analyzing and discriminating the different soft tissues with a strong sensitivity to the lipid content of the tissue.
First report on iron demand by Antarctic sea-ice algae and under-ice phytoplankton
Authors: Lannuzel Delphine , Fourquez Marion , Jong Jeroen , Tison Jean-Louis , Delille Bruno , Schoemann Véronique
Published: May 2022

Antarctic sea ice is a seasonal source of iron (Fe) to the Southern Ocean (SO), where surface waters Fe levels are otherwise generally low. The effectiveness of Fe released from melting sea ice does not only depends on the magnitude of the supply, but also on the biological Fe demand. Here, we hypothesize that Fe uptake rates by sea-ice algae and under-ice phytoplankton are higher than the rates reported for open ocean phytoplankton in the SO. We performed 55Fe and carbon (14C) short-term uptake field measurements in, on and under Antarctic sea ice. Our results show that over 90% of Fe taken up by sea-ice algae and under-ice phytoplankton was found on the outside of the algal cells. The intracellular Fe (Feintra) uptake rates were high and reached up 68, 194 and 203 pmol Fe L− 1 d− 1 in seawater, bottom ice and over-ice respectively. Overall C uptake in bottom sea ice was low, ranging between 0.03 and 3.2 µmol C L− 1 d− 1, but similar to previous sea-ice studies. The Feintra:C ratios in sea ice also increased over the 26 days times series, from 5.8 to 230 µmol Fe mol C− 1. This is well above the ranges reported for other naturally Fe-fertilized areas of the SO. As the Antarctic icescape and associated ecosystems are changing, this dataset will undoubtedly inform the parameterisation of sea-ice biogeochemical and ecological models in ice-covered regions.
Attitudes of older patients and caregivers towards deprescribing of medications in Ethiopia
Authors: Gadisa Diriba Alemayehu , Gebremariam Esayas Tadesse , Yimer Getnet , Urgesa Efa Deresa
Published: May 2022

Background: Deprescribing as the part of optimal health care is aimed at reducing the overall impact of polypharmacy on patients and health care services. Understanding how older adults and their caregivers understand deprescribing is crucial to ensuring a holistic approach to deprescribing.Objective: To assess the attitude of older patients and caregivers towards deprescribing of medication at Ambo university referral hospital.Methodology: Institutional based cross-sectional study was conducted using the revised Patient Attitude Towards Deprescribing tool (rPATD). The collected data were processed and analyzed by using a statistical package for social science (SPSS-25) and presented in tables. Backward linear regression and logistic regression was used to determine the degree of association between dependent and independent variables. 95% confidence interval and two sides P-value ≤ 0.05 was utilized for reporting. Result: One hundred fifty six (81.3%) of the respondents (i.e.85% of older and 77.2% of caregivers) agreed to stop one or more of their regular medications if the physician recommends doing so despite 98(51.0%) of them (i.e. 49% of older and 53.3% of caregivers) being satisfied with their/their care recipient’s medications. On the overall aggregate mean score, the respondents had neutral position (2.6-3.59) regarding burden and concerns to stopping medications factor score whereas majority of them disagree (1-2.59) with inappropriateness of the medication they had been received and agreed (3.6-5) with the need for their involvement in medicine decision making. Concerns to stopping medicine scores (AOR=0.440, 95% CI=0.262-0.741, P=0.035) was significantly associated with the willingness to have one or more of their regular medicine(s) deprescribed. Perceived levels of medication inappropriateness (AOR=0.653, 95% CI= 0.456-0.936, P=0.020) were significantly associated with the overall satisfaction with their medicines regimen.Conclusion: Majority of older patients and their caregivers would be willing to have their regular medication stopped if the physicians recommend it. Having higher perceived concerns for stopping the medicines and higher medicine inappropriateness factor score were the two main determinants of willingness to deprescribe and overall satisfaction with their medicine respectively. Healthcare providers should prompt the deprescribing process with older adults and caregivers in their regular clinical practice.
METTL3 suppresses anlotinib sensitivity by regulating m 6 A modification of FGFR3 in oral squamous cell carcinoma
Authors: Chen Jie , Li Shuai , Huang Zhexun , Cao Congyuan , Wang Anxun , He Qianting
Published: May 2022

Purpose: N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA, but there were few studies of its role in the cancer drug sensitivity and resistance. Anlotinib has been proved to have effective antitumor effects in oral squamous cell carcinoma (OSCC) in our previous study. Here, we sought to investigate the treatment target of anlotinib and the function and mechanisms of m6A modification in regulating anlotinib effect in OSCC.Methods: Anlotinib treatment in a dose-dependent manner, western blotting, qRT-PCR and cell lost-of function assays were used to study the treatment target of anlotinib in OSCC. RNA m6A dot blot assays，the m6A MeRIP-seq and MeRIP-qPCR, RNA and protein stability assays were used to explore the m6A modification of the treatment target of anlotinib. Cell lost-of function assays after METTL3 depletion were conducted to investigate the effect of m6A modification level on the therapeutic effect of anlotinib in OSCC. Patient-derived tumor xenograft (PDX) models and immunohistochemistry staining were performed to study the relationship of METTL3 and antitumor sensitivity of anlotinib in vivo.Results: Anlotinib targeted FGFR3 in the treatment of OSCC and inhibited tumor cell proliferation and promoted apoptosis by inactivating the FGFR3/AKT/mTOR signaling pathway. METTL3 was identified to target and modify FGFR3 m6A methylation and then decrease mRNA stability. METTL3 expression level was related to the anlotinib sensitivity in OSCC cells in vitro and METTL3 knockdown promoted anlotinib sensitivity of OSCC cells by inhibited the FGFR3 expression. PDX models samples furthermore showed that METTL3 and FGFR3 levels are tightly correlated with the anlotinib efficacy in OSCC.Conclusion: In summary, our work revealed that FGFR3 was served as the treatment target of anlotinib and METTL3-mediated FGFR3 m6A modification played a critical function in the anlotinib sensitivity in OSCC.
Bioinformatics analysis of potential biomarkers associated with diagnosis and treatment of sarcoidosis involved with different tissues
Authors: Wu Mingcheng , Zhu Yan , Han Shiyun , Kou Yan , Li Xiang , Gao Xing , Liu Hongbo , He Rui
Published: May 2022

Background
Sarcoidosis is a multisystemic granulomatous disease characterized by the formation of non-caseating granulomas, which occurs variably in organs. It is typically prevailing in lungs as well as skin and lacrimal glands. This study was aimed to demonstrate the potential etiology and pathogenesis of sarcoidosis and identify the effective biomarkers associated with the diagnosis and treatment of sarcoidosis.
Results
A total of 243 DEGs were screened in the pulmonary datasets, 141 and 389 DEGs were acquired through the skin tissue datasets and lacrimal tissue datasets respectively. In lung tissues, DEGs were mainly focused on chemokine-mediated signaling pathway, cellular response to interferon-γ, cell adhesion and chemokine activity. For DEGs in skin and lacrimal tissues were primarily related to interferon-gamma-mediated signaling pathway, immune response, integral component of membrane and MHC class II receptor activity. The result of KEGG enrichment pathway analysis revealed that DEGs were mainly enriched in interferon-gamma-mediated signaling pathway, cell adhesion molecules, Jak-STAT signaling pathway and inflammatory bowel disease. After PPI network analysis, 10 hub genes were identified, respectively.
Conclusion
This study indicated that utilizing bioinformatic methods to analyze sarcoidosis in variable situations and finding the similarities and differences in molecular mechanism under different conditions are helpful for us to understand pathogenesis of sarcoidosis in a more comprehensive way, laying the foundation for clinical diagnosis and treatment of sarcoidosis.
Effect of Preloading and Nano-Silica on Structural Behaviour of Corroded R.C. Beams
Authors: Marawan Ahmed. E. , Debaiky Ahmed. S. , Abdel-Kareem Ahmed. H.
Published: May 2022

Reinforced concrete structures are considered as permeant structures that can be used for a long time. But, one of the most issues has been discussed in construction community was corrosion of embedded steel bars. Corrosion has a negative significantly effect on the behavior of reinforced concrete structures where decrease bar cross section, formats massive products, reduces bond between concrete and steel bars and also, reduced load capacities. To simulate corrosion under loading condition, the specimens were subjected to preloading before corrosion process. Also, addition of nano-silica to concrete mixes with variable ratios was studied to show its effect on corrosion rate. 8 beams were divided into two groups (A and B) with preloading and unloading respectively. Then, all beams were corroded accelerable. 4 concrete mixes were designed. The experimental result included compressive strength of concrete, corrosion cracks pattern, steel mass loss and ultimate flexural load. Finally, it was noticed that preloading had negative effect in steel mass loss, ultimate load, and increased cracks. On contrary, addition of nano-silica improves the structural properties of corroded beams.
miR-34a, a physical exercise regulator, involved in LncRNA CCAT2 signaling to regulate hepatic stellate cells proliferation
Authors: Gao Haibing , Ma Huaxi , Wang Qiaowen , Lin Shenglong , Wang Xiangmei , Zhang Dongqing , Wu Wenjun , Liao Ziyuan , Chen Mengyun , Lin Huiming , Xie Jinming , Li Qin , Ye Hanhui , Lin Minghua , Li Dongliang
Published: May 2022

In plasma, miR-34a could be one of potential biomarkers for frailty and is involved in the physiology processes which are benefit from exercise. One of its targets, Smad4 play important role in TGF-β1 pathway which is a dominant factor for balancing collagen production and degradation in hepatic stellate cells. TGF-β1/Smad4 regulated collagen deposition is a hallmark of hepatic fibrosis. Thus, miR-34a could be a link between exercise and hepatic disease. The potential regulation on miR-34a by LncRNAs in hepatic stellate cells (HSCs) is still reserved to be revealed. In current study, it was hypothesized that a miR-34a interactor, lncRNA CCAT2 may regulate TGF-β1 pathway in liver fibrotic remodeling. Dual luciferase activity showed CCAT2 and Smad4 are targets of miR-34a-5p. Sh-CCAT2 transfection prohibit HSCs proliferation and induce HSCs apoptosis, also inhibited ECM protein synthesis in HSCs. Decreased miR-34a-5p enhanced HSCs proliferation, blocked HSCs apoptosis and promoted ECM protein production. miR-34a-5p inhibitor undo protective regulation of sh-CCAT2 in liver fibrosis. Furthermore, clinical investigation showed that CCAT2 and Smad4 expression level were significantly induced, while miR-34a-5p was significantly decreased in HBV related liver fibrosis serum. In conclusion, activated HSCs via TGF-β1/Smad4 signaling pathway was successfully alleviated by CCAT2 inhibition through miR-34a-5p elevation.
Efficacy and safety of PARP inhibitors in the treatment of BRCA-mutated breast cancer: An updated systematic review and meta-analysis of randomized controlled trials
Authors: Sun Xiaoyu , Xu Suying , Li Yiming , Lv Xuemei , Wei Minjie , He Miao
Published: May 2022

Background: Poly-ADP-ribose polymerase inhibitors have emerged as a new class of therapeutic agents for breast cancer patients with BRCA mutations; however, the efficacy and toxicity of PARP inhibitors have not been clearly established.Methods: This study comprehensively evaluated the efficacy and safety of PARP inhibitors in BRCA mutated breast cancer patients. Online databases were systematically searched, and six clinical trials were included in the meta-analysis. The primary endpoint of efficacy was PFS, secondary endpoints are OS and ORR. In addition, we also assessed safety.Results: The results of the meta-analysis showed that PARP inhibitors can effectively improve the PFS, and OS of patients compared with the control group. The pooled HR (PARP inhibitor vs control group) was 0.63 (95 % CI, 0.55− 0.73) in PFS and 0.83 (95% CI, 0.73 -0.95) in OS among all patients. In terms of safety, PARP inhibitors show controllable adverse reactions. There were no significant differences in overall AEs or grade≥3 AEs between the PARP inhibitor arms and the control arms. Conclusions: In general, this study demonstrates PARP inhibitors perform well in both monotherapy and combination therapy, not only can provide substantial survival benefit, but also do not increase the additional toxicity burden, and the clinical application is promising.
MCluster-VAEs: an end-to-end variational deep learning-based clustering method for subtype discovery using multi-omics data
Authors: Rong Zhiwei , Song Jiali , Cao Lei , Liu Zhilin , Yu Yipei , Qiu Mantang , Hou Yan
Published: May 2022

Background
The discovery of cancer subtype based on unsupervised clustering helps provide precise diagnoses, guide treatment and improve patients’ prognoses. Instead of single-omics data, multi-omics data can improve performance of the clustering because it obtains a comprehensive landscape for understanding biological systems and mechanisms. However, heterogeneous data from multiple sources raises high complexity and different kinds of noise, which will be detrimental to the extraction of clustering information.
Methods
We propose an end-to-end deep learning-based method, Multi-omics Clustering Variational Autoencoders (MCluster-VAEs), that can extract cluster-friendly representations on multi-omics data. First, unified network architecture with an attention mechanism is developed for modeling multi-omics data precisely. Then, using a novel objective function built from the Variational Bayes technique, the model is trained to effectively obtain the posterior estimation of clustering assignments.
Results
Compared with twelve other state-of-the-art multi-omics clustering methods, MCluster-VAEs achieved outstanding performance on benchmark datasets from the TCGA database. On the Pan Cancer dataset, MCluster-VAEs achieved adjusted Rand index of around 0.78 for cancer category recognition, an increase of more than 18% compared with other methods. Furthermore, the survival analysis and clinical parameters enrichment tests on ten cancer datasets demonstrate that MCluster-VAEs delivered comparable or even better results than many typical integrative methods.
Conclusions
These results demonstrate that MCluster-VAEs is a new powerful tool for dissecting complex multi-omics relationships and providing new insights for cancer subtype discovery.
Nicotine Metabolism and Genetic Polymorphism Cyp2a13 in Male Smokers in Indonesia
Authors: Soeroso Noni Novisari , Soliha Chaliza , Ananda Fannie Rizki , Zain-Hamid Rozaimah , Bihar Syamsul
Published: May 2022

BACKGROUND: The rate of nicotine metabolism described the presence of nicotine metabolites, which are the negative impact of cigarette smoke. CYP2A13 is one of the main enzymes responsible for nicotine metabolism and xenobiotic activity in tobacco smoking-related lung cancer.AIM: This study aims to analyze the correlation between CYP2A13 and nicotine metabolism in male smokers in Indonesia.METHODS: This was a cross-sectional study with consecutive sampling to 100 male smokers aged between 20 and 65 years old meeting inclusion and exclusion criteria. The CYP2A13 polymorphism was examined by restriction fragment length polymorphism (RFLP) PCR through venous blood extraction. The levels of nicotine metabolites in the urine samples were assessed by high-performance liquid chromatography (HPLC). The associations between nicotine metabolism and genetic polymorphism of the CYP2A13 gene in male smokers in Indonesia was determined by logistics regression test using Epi Info-7 software.RESULTS: There were 100 participants involved in this study, in which 78 subjects were with the first stage of CYP2A13 polymorphism. There was no significant correlation between CYP2A13 genotype and nicotine metabolism (p value > 0.05). The CC genotype was more frequently found in the population in this study. Most research subjects had rapid metabolizers.CONCLUSION: There is no significant relationship between CYP2A13 polymorphism and nicotine metabolism in male smokers in Indonesia. Therefore, it is important to carry out further studies to investigate genetic polymorphisms and nicotine metabolism in different population.
Scientific trends and knowledge structures of exosomes from macrophages: a bibliometric analysis
Authors: Liu Yi , Zheng Bowen , Zhong Yuan , Liu Yi
Published: May 2022

Background:Exosomes from macrophages present unique roles in body systems and regulate inflammation or physiological processes. A bibliometric analysis may reveal topic patterns of macrophage-derived exosomes that can be used to investigate future research.Objectives:The aim of this study was to explore the research trends and knowledge structures of macrophage-derived exosomes during past 11years.Materials and methods: Literature related to exosomes from macrophages was scanned in the PubMed database, with a period of 2011 to 2021. The analysis retrieved 2457 records and performed high-frequency major MESH terms/MESH subheadings extraction, biclustering analysis, strategy map analysis, and social network analysis.Results: Cluster analysis yielded 5 categories in which the rather mature clusters in the past 11 years are mainly about bioengineering, therapeutic methods, and osteoclast-related metabolism. Tumor-associated macrophages and exosomes, as well as the regulation of the immune system, are discussed in Cluster 1 and 2, which possess great potential for advancement. Cluster 3 focuses on the interaction of mesenchymal stem cell exosomes with macrophage cytology. Extracellular Vesicles/immunology; Exosomes/transplantation; Mesenchymal Stem Cells/cytology; and other terms around the network are all possible future research hotspots, according to the social network analysis.Conclusion: Research topics such as tumor-associated exosomes, exosome physiology, and exosomes/transplantation still deserve deep research. Further research should expand on new topics such as exosomes and macrophages in the tumor environment, exosomes from mesenchymal stem cells, and cell-free therapy.
Assessment of Surface Irrigation Potential Availability Using Gis in Gilgel Abbay Catchment; Ethiopia
Authors: Sintayehu Gashaw , Temesgen Edmealem , Akili Destaw
Published: May 2022

Irrigation is an important investment for improving rural income through increased
agricultural production. The expansion of irrigation and effectively manage agricultural water holds significant potential to enhance productivity and reduce vulnerability to the climactic
volatility in any country. Investigation of available water resources and potentially irrigable land is essential for the development of irrigated agriculture. This study was concerned with the assessment of surface irrigation potential availability in the Gilgel Abay watershed by implementing Arc GIS 10.1. Assessment of land suitability for irrigation is essential for the long production of crops and food security of the ever-growing population, as well as for the efficient use of limited physical land resources in the studied area. This research focuses on the possibilities for catchment surface irrigation and a water-saving sowing time scenario. The physical and chemical properties of the soil, slope, LULC, distance from water sources (Proximity to water), and surface water resource availability were all considered while determining land suitability for surface irrigation. According to the results of the land suitability evaluation ratings based on quantitative and qualitative land suitability for surface irrigation, 22.59 percent (86,747.19 ha) of lands in the research region were in the high to marginally suitable classes, while 77.41 percent were in the non-suitable class (297,252.4 ha). For November, December, January, and February sowing time scenarios, total irrigation water demand is 5,927.5Mm3, 370.2 Mm3, 455.4 Mm3, and 506.2 Mm3 respectively accordingly to irrigate 86961.24ha of irrigable land for 10 selected and dominating crops. The most favorable sowing starting month, according to sowing time scenarios, is in December, in order to save water or use less water to irrigate all available irrigable land and to fulfill all selected and dominating crops in the research area. Therefore, as a result, this research will assist all participants in making irrigation investment decisions and identifying long-term irrigation investment prospects in the study area.
The Quantitative Evaluation of Retinal Layers After Resolution of Subretinal Fluid in Acute Central Serous Chorioretinopathy
Authors: Dursun Erdem , Dursun Gamze Akyuz
Published: May 2022

Purpose: To evaluate the average retinal layer thicknesses in eyes with unilateral acute central serous chorioretinopathy (CSC) (with subretinal fluid (SRF)) and after complete resolution of SRF in these eyes and to compare the results with those obtained in healthy eyes.Methods: Fifty-four eyes of 27 patients with unilateral acute CSC who had complete resolution of SRF and 25 eyes of 25 healthy control subjects enrolled in this retrospective study. The average thicknesses of the retinal layers were measured by segmentation analysis of optical coherence tomography at baseline and 6 months after complete resolution of SRF.Results: The mean outer nuclear layer (ONL) thickness was significantly lower in eyes with CSC than in fellow eyes (p<0.001). The mean ONL thickness was increased after resolution of SRF, but still low compared to unaffected fellow eye and the increment was not statistically significant (p>0.05). There were significant correlations between visual acuity and ONL thicknesses at baseline and 6 months after complete resolution of SRF (p<0.001, r=-0.810; p<0.001, r=-0.705, respectively).Conclusion: ONL thickness is thinned in cases with acute CSC, and although there is some increment in ONL thickness 6 months after complete resolution of SRF, it is still thinner compared to unaffected fellow eyes.
A hybrid Latent Dirichlet Allocation - BERT approach for topic discovery of market places
Authors: Bouabdallaoui Ibrahim , Guerouate Fatima , Bouhaddour Samya , Saadi Chaimae , Sbihi Mohamed
Published: May 2022

The tourism industry is now intimately linked to the web, as It was one of the first industries to fit on digital transformation. The tourist is more autonomous in organizing and preparing his trip, and the possibilities of leaving at competitive prices are numerous. New technologies have an impact on tourism and it is now necessary to think about communication and marketing accordingly. Market places in Morocco are reached by millions of tourists each year. Tourists share their experiences in social medias to encourage or discourage other tourists who are interested in visiting such places. The main goal of this work is to propose a hybrid architecture based on Latent Dirichlet Allocation (LDA) and Bidirectional Encoder Representations from Transformers (BERT) with a latent space representation technique to perform topic modeling and have as a result an idea of each tourist's review and particularly what he thinks about a specific market place in Morocco.
Multi-organs toxicities induced by anti-tubercular drugs: A preclinical experimental study
Authors: Ahmed Akheruz Zaman , Bhat Nandini Prashanth , Kalthur Sneha Guruprasad
Published: May 2022

This study was aimed to observe the multiple organ toxicities induced by different anti-tubercular drug resistant groups like isoniazid resistance, rifampicin resistance, multidrug resistance including drug susceptible anti-tubercular drugs and their time of recovery from the toxicities induced by these drugs. Wistar Albino mice were treated with drug susceptible anti-tubercular drug (Isoniazid, Rifampicin, Ethambutol & Pyrazinamide), Isoniazid resistance anti-tubercular drugs (Kanamycin, Levofloxacin, Rifampicin, Pyrazinamide & Ethambutol), Rifampicin resistance anti-tubercular drugs (Kanamycin, Levofloxacin, Ethionamide, Cycloserine, Isoniazid, Pyrazinamide & Ethambutol), Multidrug resistance anti-tubercular drug (Kanamycin, Levofloxacin, Ethionamide, Cycloserine, Pyrazinamide & Ethambutol). Animals were sacrificed after giving two weeks recovery gap from the last drug treatment. To understand the late effects, mice were sacrificed after giving two months recovery gap from the last drug treatment. Histopathology of internal organs was done by H & E and PAS. Bone marrow cells were stained with Acridine Orange dye to detect micronucleus and apoptotic cells. Expression of γ-H2AX in bone marrow cells were done by immunohistochemistry. In liver moderate to severe type of toxicities were observed in all groups in the form of nuclear alteration, sinusoidal dilation, vacuolization, necrosis, WBC infiltration. In kidney we had observed mesangial cell proliferation, vacuolization, WBC infiltration, dilation of Bowman’s space. The severity of toxicity was more at short term recovery group than long term recovery groups. Drug susceptible anti-tubercular drugs (INH, RIF, and EMB & PZA) had shown more toxic in compared to other anti-tubercular drugs.
Assessment of the Informed Consent Process in the Provision of Dental Care in Mulagohospital, Uganda
Authors: Nono- David , Mapley Edward , Rwenyonyi Charles Mugisha , Okullo Isaac
Published: May 2022

Background: Informed consent is grounded in the principle of autonomy and represents patients’ rights to participate in clinical decisions regarding their treatment. It is equally an ethical and legal requirement in dental care. The dental practitioner must offer appropriate information about all aspects of the treatment and ensure that a patient understands and makes an informed decision. There is limited literature on informed consent for dental care in Uganda. The aim of the study was to assess patients’ comprehension of the informed consent process and dental practitioners’ practices in obtaining informed consent.Methods: This was a cross-sectional descriptive study conducted in the Dental Outpatient Department of Mulago Hospital. Two separate questionnaires were employed to collect data from dental patients and dental practitioners, respectively. Data were entered into Epi-data, coded and imported into STATA 14 for statistical analysis.Results: Overall, the level of patients’ comprehension of the informed consent process was 91.1%, with 96.3% who felt the dental practitioners satisfactorily explained to them the treatment received and, 65.1%understood very well the information given to them. About 93.5% of the patients confessed that they were given other options of treatment while 98.5% consented before the dental practitioners started treatment. Most (94.7%) dental practitioners followed good clinical practices in obtaining informed consent and 98.7% gave information before initiation of treatment while 85.3% obtained consent from patients before starting any procedures. However, only 4 (5.3%) of the dental practitioners obtained written informed consent from patients. Conclusion: There is a need to devise ways of improving patients' understanding of the treatment information given to them to support them make better and informed decisions regarding their care. Dental practitioners need to put more emphasis on the use of written consent in dental care because documentation helps in providing accountability and protects dentists from medical litigation in case the patients were to sue them for any treatment-related complications.
Application of Analytic Hierarchy Process: Key Factors of an Environment-related Gender Assessment Project
Authors: Chen You-Ning , Tseng Chao-Heng , Hsieh Ming-Lun
Published: May 2022

Gender issues have become a sustainable development goal under the UN auspices. Gender assessment projects are more likely to face gender differences and create corresponding policies, legislations, or treatments. Shortcomings in gender assessment projects include the impact of environmental issues on gender studies. Recently, natural disasters and air pollution incidents have been frequent. The environmental field has gradually focused on gender and environmental issues. However, domestic and foreign environment-related gender assessment projects primarily use organisational gender structure, gender income, and political participation rates as the primary assessment items. They lack environment-related gender assessment projects. This study collected 100 related studies, which were filtered into 89 articles, comprehensively integrating four assessment dimensions, eight perspectives, and 16 assessment projects. Further, through a questionnaire survey and analytic hierarchy process AHP) analysis, the study determined the key factors of an environmental-related gender assessment project. The key factors were working environments and climate change, especially related to occupational disease and high-temperature disease, emphasising mortality and prevalence rates. Therefore, gender assessment projects should prioritise establishing assessment projects and statistical indicators of the working environment and climate change perspectives and implement them in corresponding gender and environmental policies, legislations, or disposals.
Insect-mediated pollination improves fruit quality of strawberries in an urban environment
Authors: Blareau Elsa , Sy Pauline , Daoud Karim , Requier Fabrice
Published: May 2022

Pollination services provided by a diversity of pollinators are critical in agriculture since they enhance the yield of many crops. However, few studies have assessed pollination services in urban agricultural systems. We performed flower-visitor observations and pollination experiments on strawberries, Fragaria × ananassa, in an urban area of Paris, France, in order to assess the effects of (i) insect-mediated pollination service and (ii) potential pollination deficit on fruit set and fruit quality (size, weight, malformation and seed set). Flower-visitor observations revealed that the pollinator community was solely comprised of unmanaged pollinators, despite the presence of apiaries in the surrounding landscape. Based on the pollination experiments, we found that the pollination service mediated by wild insects improved fruit size as a qualitative value of production, but not fruit set. We also found no evidence for pollination deficit in our urban environment. These results suggest that the local community of wild urban pollinators is able to support strawberry crop production, and thus plays an important role in providing high quality, local and sustainable crops in urban areas.