bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of novel benzylidenecyclohexenones derivatives as potential anti-cancer inhibitors using 3D-QSAR, pharmacokinetics, and molecular docking studies.
Authors: Er-rajy Mohammed , Mrabti Nidal Naceiri , Zarougui Sara , Elhallaoui Menana
Published: April 2022

The 3D-QSAR models were established in this study based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA), the optimal CoMFA model established gave \({\text{Q}}^{2}\)= 0.671, \({\text{R}}^{2}\)= 0.925 and \({\text{R}}_{\text{p}\text{r}\text{e}\text{d} }^{2}\)= 0.868, and the best CoMSIA/SEA model gave \({\text{Q}}^{2}\)= 0.627, \({\text{R}}^{2}\)= 0.775, and \({\text{R}}_{\text{p}\text{r}\text{e}\text{d} }^{2}\)= 0.962. The predictive ability of the developed models was evaluated by external and internal validation. In this study, steric, electrostatic, and hydrogen bond acceptor fields played a key role in the anti-cancer activity. Molecular docking results theoretically revealed the importance of residues ARG164 and THR45 in the active site of the TrxR enzyme. Based on these results, we designed several new inhibitors, and their inhibitory activities were predicted by the best model (CoMFA). In addition, these new inhibitors were analyzed for their ADMET properties and their similarity to drugs. These results will be of great help for the optimization of new anti-cancer drug discovery.
Comprehensive analysis of negatively correlated miRNA-mRNA regulatory pairs associated with breast cancer diagnosis
Authors: Xia Tiansong , Li Jiaying , Fan Xingchen , Zou Xuan , Liu Cheng , Wang Tongshan , Peng Shuang , Zhu Wei
Published: April 2022

Purpose： MicroRNAs (miRNAs) represent small noncoding RNAs controlling mRNA expression. MiRNA and mRNA amounts in matching specimens were utilized for identifying miRNA–mRNA interactions. Transcriptome, immunophenotype, methylation, mutation, and survival data analyses were integrated to examine the profiles of miRNAs and target mRNAs and their associations with breast cancer (BC) diagnosis.Methods: Based on the mRNA/miRNA expression microarray and RNA-Seq data sets in the GEO database and RNA-Seq data in TCGA, we analyzed differential expression profiles through GEO2R and the R language. Differentially expressed miRNAs and targeted mRNAs were screened from experimentally verified miRNA-target interactions databases by Pearson's correlation analysis. qRT-PCR was used for verification in breast cancer and benign disease samples, and logistic regression analysis was utilized to establish a diagnostic model based on miRNAs and target mRNAs. ROC curve analysis was performed to test the ability to recognize miRNA-mRNA pairs. Then, complex interactions of miRNA-mRNA regulatory pairs and phenotypic hallmarks, including tumor-infiltrating lymphocytes, tumor microenvironment, tumor mutation burden and global methylation, were described.Result: We first identified 27 dysregulated miRNAs and 135 dysregulated mRNAs based on five gene expression and 21 miRNA expression data sets from GEO and RNA-Seq data from TCGA. Utilizing Pearson's correlation analysis, ten negative miRNA-mRNA regulatory pairs were identified after screening in TarBase and miRTarBase databases, and related miRNA and target mRNA amounts were assessed in 40 breast cancer tissue and 40 breast benign disease tissue. Finally, 2 key regulatory pairs (miR-205-5p/HMGB3 and miR-96-5p/FOXO1) were selected to establish a diagnostic model. We next analyzed the functions of these four markers in breast cancer.Conclusions: A diagnostic model including two miRNAs and their respective target mRNAs was established to distinguish BCs and benign breast diseases. These markers play an essential role in the pathogenesis of BC.
Effectiveness of acrylonitrile-co-methallyl sulfonate surface-treated membranes for treating pneumonia: A propensity-score matched retrospective cohort study
Authors: Hayashi Kentaro , Sasabuchi Yusuke , Matsui Hiroki , Nakajima Mikio , Ohbe Hiroyuki , Fushimi Kiyohide , Ono Kazuyuki , Yasunaga Hideo
Published: April 2022

Background: The acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has cytokine adsorption capacity and is used for treating sepsis. This study aimed to compare the effects of continuous renal replacement therapy (CRRT) using the AN69ST membrane with CRRT using other membranes for patients with pneumonia-associated sepsis.Methods: We conducted a retrospective cohort study using a nationwide Japanese inpatient database. We included data of those adults who were hospitalized with a primary diagnosis of pneumonia and received CRRT using either the AN69ST membrane or another membrane within 2 days of admission and were discharged from the hospitals between September 2014 and March 2017. Propensity-score matching was used to compare in-hospital mortality between the two groups.Results: Eligible patients (N = 2,393) were categorized into an AN69ST group (N = 631) and a non-AN69ST group (N = 1,762). The overall in-hospital mortality rate was 38.9%. Among the 545 propensity-matched patient pairs, the in-hospital mortality rate was significantly lower in the AN69ST group than in the non-AN69ST group (35.8 vs. 41.8%, P = 0.046).Conclusions: Among patients with pneumonia-associated sepsis treated with CRRT, CRRT with the AN69ST membrane was associated with a significantly lower in-hospital mortality than CRRT with standard membranes.
The Hypothalamic-Pituitary-Gonad Axis in Male Cushing’s disease Before and After Curative Surgery
Authors: Zheng Hangping , Wang Qi , Cui Qiaoli , Sun Quanya , Wu Wei , Ji Lijin , He Min , Lu Bin , Zhang Zhaoyun , Ma Zengyi , Shen Ming , Shou Xuefei , Wang Yongfei , Zhao Yao , Li Yiming , Ye Hongying , Zhang Shuo
Published: April 2022

Objective: Gonadal and sexual disturbances are commonly encountered in patients with Cushing’s disease. Nevertheless, the prevalence of hypogonadism in male Cushing’s disease, the risk factors as well as the recovery time have been scarcely reported. Therefore, we aimed to explore the prevalence of hypogonadism at baseline and its determinants. In addition, the recovery time of hypogonadism and risk factors for unrecovered gonadal axis in male Cushing’s disease with biochemical remission were investigated.Methods: We reviewed medical records of males with Cushing’s disease managed between 2010 and 2020. Fifty-two male patients were enrolled according to the criteria. Each case attained biochemical remission after transsphenoidal surgery. Demographic details, clinical features, 24-hour UFC, hormonal profile [serum PRL, FSH, LH, TT, ACTH, cortisol, TT4/FT4, TT3/ FT3, TSH and IGF-1] were measured at baseline and during follow-up. The maximal tumor diameter on MRI was recorded at diagnosis.Results: Hypogonadotropic hypogonadism was observed in thirty-nine patients (75%) at diagnosis. Total testosterone was negatively correlated with ACTH and 24-hour UFC. Midnight serum ACTH level at diagnosis was significantly associated with hypogonadism after adjusting for confounding factors. Thirty-two (80%) patients achieved eugonadism within 12 months after the surgery, of which twenty-eight (87.5%) achieved eugonadism within 3 months. Seven patients were persistently hypogonadal during the follow-up (>1 year), mainly due to the hypopituitarism as a complication of the therapies such as surgery.Conclusion: Hypogonadotropic hypogonadism is frequent in male Cushing’s disease, but it is reversible in most cases within one-year follow-up after remission.
Assessment of farmers’ socioeconomic and conservation practice towards watershed management in the South West of Ethiopia
Authors: Woldeab Bizuneh , Ambelu Argaw , Beyene Abebe , Efrem Zewdu , Deribe Siyoum , Megersa Moa , Alemu Tibebu , Mereta Seid Tiku
Published: April 2022

Background
Watershed resource conservation is important for the wellbeing of the environment and communities. Understanding farmers’ socioeconomics and watershed conservation practices help in determining necessary interventions to address environmental threats. The study area is important at regional and national level due to the hydroelectric dam of the mega power project. This study deals with the farmers’ socio economic and conservation practices of Gilgel Gibe watershed. The study targeted 305 households in 4 districts of Jimma Zone surrounding the Gilgel Gibe Reservoir I. Semi-structured questionnaire was administered via interviews and focus group discussions led by trained survey interviewers.
Result
The findings of the study indicated that majority of farmers in the watershed have adequate knowledge, positive attitude and bad practice towards watershed conservation. To achieve better means of subsistence and improve their living condition farmers are forced to put stress on natural resource, degrading watershed and increase pollution loads that affect water quality of tributaries and reservoir.
Conclusion
Based on the present scenario, we forwarded stakeholders to establish team from the elders, officials at woreda and zonal level to initiate commitment, coordinate conservation activity and promote households’ income generating activities at homestead level like conservation agriculture.
Preparation and Validation of Ultra-sensitive Aptamers by Computer Simulation and Site- specific Mutation
Authors: Sha Junyi , Lin Hong , Zhang Ziye , Sui Jianxin
Published: April 2022

Aptamers are widely used in the detection field as a new type of probe due to their advantages of easy synthesis and modification. Due to the traditional aptamer screening method, the aptamers which are screened by SELEX technology generally have redundant sequences, which affect the binding affinity and detection sensitivity. In this study, a structural transformation strategy for rationally shortening was established by analyzing the secondary structure, finding the sequence of the binding site by base mutation and double cloning the binding sites. We obtained a 27-mer new aptamer SEQ.A52 with the dissociation constants (Kd) of 10.74 nM which is 21 times higher than the original aptamer. When used to detect enrofloxacin(ENR) with fluorescent method, the sensitivity could reach to 50 ~ 1000 pM and the limit of detections(LOD) was only 41.35 pM which was 88 times higher than the original aptamer. All the results implied that the strategy could be used for structural modification of some other aptamers to increase the affinity and sensitivity.
Preferential substrate use decreases priming effects in contrasting treeline soils
Authors: Michel Jennifer , Hartley Iain P. , Buckeridge Kate M. , Meegen Carmen van , Broyd Rosanne , Reinelt Laura , Quispe Adan J. Ccahuana , Whitaker Jeanette
Published: April 2022

In high altitudes and high latitudes climate change manifests in upward and northward shifting treelines. This entails changes to the carbon (C) and nitrogen (N) composition of organic inputs to soils and can increase or decrease microbial mineralisation of native soil organic matter (positive or negative priming effect). It is currently unknown whether the observed treeline shifts will lead to carbon loss or storage in the soils of these ecosystems.
We therefore investigated priming effects in treeline soils from high altitudes (Peruvian Andes) and high latitudes (subarctic Sweden). In a laboratory soil incubation, we added realistic amounts of organic carbon at a constant ratio of 30% substrate-C to each soils’ microbial biomass C. Substrate additions were neutral in pH and covered different C:N ratios, representing naturally occurring substances of the studied ecosystems.
We observed a clear pattern linking the direction of priming (positive or negative) to land cover (boreal or tropical forest, tundra heath, Puna grassland) and soil horizon (organic or mineral). Mechanistically, no support was found for N-mining to induce positive priming, indeed half of all priming effects were negative. Whenever negative priming prevailed, the decrease in SOM-mineralisation was consistently linked to increased microbial substrate utilisation.
In line with other recent studies, our results suggest preferential substrate use is pervasive, linked to negative priming and a promising tool to increase soil carbon storage. Yet, the positive priming observed alerts climate change-induced upwards shifts in high altitudes and deeper rooting plants in high latitudes may cause C-loss via positive priming.
Efficacy of Cholecalciferol rodenticide against Wood Rat, Rattus tiomanicus and its secondary poisoning impact towards Barn Owl, Tyto javanica javanica
Authors: Noh Ariff Ateed Mohd , Ahmad Abu Hassan , Salim Hasber
Published: April 2022

Studies were conducted on the potential use of cholecalciferol as an alternative to anticoagulant rodenticides against common rat pest in oil palm plantations, i.e., wood rats, Rattus tiomanicus, and the secondary poisoning impact of cholecalciferol on barn owls, Tyto javanica javanica. The laboratory efficacy of cholecalciferol was compared with commonly used first-generation anticoagulant rodenticides (FGARs): chlorophacinone (0.005% a.i) and warfarin (0.05% a.i). The results of the study showed cholecalciferol baits recorded high mortality at 71.39% against wild wood rats in six-day feeding laboratory trial. Similarly, the FGAR chlorophacinone recorded a high mortality rate of 74.20%. Warfarin baits recorded the lowest mortality rate at 46.07% against the rat samples. The days-to-death of rat samples was in range of 6-8 days. The highest daily consumption of bait by rat samples was recorded by warfarin at 5.85±0.38 gram per day while the lowest was recorded in rat samples fed with cholecalciferol, i.e., 3.03±0.20 gram per day. Chlorophacinone-treated and control rat samples recorded consumption of about 5 gram per day. A secondary poisoning assessment on barn owls in captivity fed with cholecalciferol-poisoned rats showed after 7 days of alternate feeding, the barn owls appeared to remain healthy. All the barn owls fed with cholecalciferol-poisoned rats survived the 7-day alternate feeding test and throughout the study, up to six months after exposure. All the barn owls did not show any abnormal behavior or physical change. The barn owls were observed to be as healthy as the barn owls from the control group throughout the study.
Comprehensive Analysis of the Expression and Prognosis Value of Claudin Family Members in Clear Cell Renal Cell Carcinoma
Authors: dang qihua , Chen Rui , Xu Jingjing , Jiang Ke , Lin Yun , He Miaoxia
Published: April 2022

Background
Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all renal cancers and has a poor prognosis. The claudin (CLND) family comprises a group of transmembrane proteins associated with tight junctions (TJs). Studies have found that the abnormal expression of CLNDs can influence TJ-function and plays an important role in the occurrence, development, and metastasis of malignant tumors in a variety of epithelial malignant tumors. However, the roles of the different CLND family members in ccRCC are poorly understood.
Results
Using the GEPIA, UALCAN, HPA, Kaplan-Meier Plotter, cBioPortal, String-DB, GeneMANIA, Metascape, and TIMER databases, we found that the expression levels of CLDN7, 8, 10, 11, 14, 16, and 19 were significantly reduced in ccRCC-affected tissues than in healthy kidney tissues. Promoters were hypermethylated in ccRCC cells. ccRCC patients with low expression levels exhibited a strong association with the clinical cancer stage, tumor grade, and poor overall survival. The functions of the differentially expressed CLDNs were primarily associated with epithelial cell differentiation and regulation of cell adhesion. Moreover, differential expression were significantly correlated with the infiltration of diverse immune cells, including six types of CD4 + T cells, macrophages, neutrophils, B cells, CD8 + T cells, and dendritic cells in ccRCC.
Conclusions
CLDN family members are expected to serve as biomarkers for predicting the prognosis of ccRCC patients.
Exercise therapy with multiple myeloma patients: Evaluation of real-life data from an oncologic care structure on feasibility, adherence, and efficacy
Authors: Wefelnberg Michael Mendes , Niels Timo , Holtick Udo , Jundt Franziska , Scheid Christoph , Baumann Freerk T.
Published: April 2022

Purpose: Multiple myeloma (MM) is a severe hemato-oncological disease with high mortality and increasing incidence rate. Since evidence on exercise therapy in MM patients remains limited, this study examines feasibility, adherence, and efficacy based on real-life data from an oncologic care structure.Methods: A data evaluation of MM patients who participated in the oncologic exercise and movement therapy (OTT) at the Cologne University Hospital between 2012 and 2019 was conducted. The patient flow was incrementally reduced to four cohorts, intention-to-treat cohort (ITTC), safety cohort (SC), adherence cohort (AC) and efficacy cohort (EC). Cohorts were evaluated descriptively and by means of correlation analysis as well as group and, time comparisons. Results: 30 patients registered at the OTT between 2012 and 2019 (ITTC). The SC (N = 26) attended exercise therapy on average about one session per week over a period of eight month. One third dropped-out within three months. In the AC (N = 15) BMI at baseline exhibited a strong and very significant negative correlation with exercise adherence. In the EC (N = 8), a significant improvement in physical functioning and a tendency towards significance in fatigue reduction between two measurement points was observed. No adverse events were documented. Conclusions: The present study reveals safety, feasibility and promising findings on adherence and efficacy of exercising MM patients under real-life therapy circumstances. Potential obstacles to exercising such as high BMI might indicate hints for future research. Improvements in physical functioning and tendencies in fatigue reduction should be examined in confirmatory study designs.
Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study
Authors: Pignon Baptiste , Peyre Hugo , Ayrolles Anaël , Kirkbride James , Jamain Stéphane , ferchiou AZIZ , Richard Jean-Romain , Baudin Grégoire , Tosato Sarah , Jongsma Hannah , De Haan Lieuwe , Tarricone Ilaria , Bernardo Miquel , Velthorst Eva , braca mauro , Arango Celso , Arrojo Manuel , Bobes Julio , Del-Ben Cristina , Forti Marta di , Gayer-Anderson Charlotte , Jones Peter , Lasalvia Antonio , Menezes Paulo , Quattrone Diego , Sanjuan Julio , Selten Jean-Paul , Tortelli Andrea , Llorca Pierre Michel , Os Jim van , Rutten Bart , Murray Robin , Morgan Craig , Leboyer Marion , Szoke Andrei , Schurhof Franck
Published: April 2022

Gene x environment (GxE) interactions have not been reliably established regarding etiology of psychotic disorders, while genes-environment (G-E) associations have been displayed. We studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the polygenic risk scores for schizophrenia (PRS-SZ) on subclinical psychosis in a population-based sample. Data were drawn from the EU-GEI study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (N = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. For each dimension, the interactions between genes and environment were assessed comparing explained variances of “Genetic” models (solely fitted with PRS-SZ), “Environmental” models (solely fitted with each environmental stressor), “Independent” models (with PRS-SZ and each environmental factor), and “Interaction” models (with an interaction term between the PRS-SZ and each environmental factor). There were no direct G-E associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except for low social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension. This study in healthy individuals suggests that i) the etiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, ii) genetic and environmental factors have independent effects on the level of this positive dimension, iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.
Spatial Analysis of Malaria Hotspots in Dilla Sub-Watershed: Western Ethiopia
Authors: Ofgeha Gemechu Y.
Published: April 2022

The study was aimed to examine the spatial variations in malaria hotspots along Dilla sub-watershed in western Ethiopia based on environmental factors for the incidences; and compare risk level among districts and their respective kebeles. Ethiopian Central Statistical Agency based meteorological data, digital elevation model, soil and hydrological data were used. Different spatial analysis tools and Software were used for watershed delineation, generating malaria risk map for all variables, reclassification of factors, weighted overlay analysis and generation of risk maps. The findings of the study reveal that all districts and kebeles have different level of malaria risk due to variation in their environmental conditions. Accordingly, significant areas in Guliso, Aira, Boji Chokorsa, Boji Dirmaji, Jarso, Najo, Gawo Kebe, and Dale Wabera are characterized as high and moderately exposed to malaria risk. More specifically, about 14 kebeles of Aira, 12 kebeles of Guliso, 8 kebeles of Jarso, 8 kebeles of Najo, 4 kebeles of Boji Chokorsa, 4 kebeles of Boji Birmaji were highly and moderately exposed to the risk. In general, out of the total area of the watershed which accounts 2773 km2, about 54.8% (1522km2) identified as high and moderate malaria risk area. The research output may help the government and humanitarian organizations to prioritize the interventions based on identified spatial variations in malaria severity. The research is aimed only for hotspot analysis which may not provide comprehensive account for community’s vulnerability to malaria. Thus, this research finding needs to be integrated with the socio-economic and other data for better malaria management in the area.
How the policy and stewardship landscape of the National Health Research System looks like in a developing country like Iran: a qualitative study
Authors: Poursheikhali Atousa , Alkhaldi Mohammed , Dehnavieh Reza , Haghdoost AliAkbar , Masoud Ali , Noorihekmat Somayeh , Cheshmyazdan Mohammad Reza , Bamir Mousa
Published: April 2022

Background: The health research system is an important national priority that requires a systematic and functional approach. Evaluating the HRS of Iran, as a developing country, and identifying its challenges show the significant role of the stewardship-related ones in how the whole system is operating well. The study aims to assess the health research system regarding stewardship functions and highlighting the enhancement points. Methods: This study was carried out between March 2020 to April 2021 using a systematic review and meta-synthesizing of evidence to examine the Iranian HRS stewardship challenges and interview 42 stakeholders, using a critical case sampling and snowballing approach that some were semi-structured and some in-depth. The interviewees were selected criteria-based, covering the policymakers, managers, research bodies, and NGOs in health research-related fields like higher education, research, technology, innovation, and science. All data were analyzed using the content analysis leading to determining eight main groups of findings under three levels of Macro, Meso, and Micro.Results: Analyzing the findings leads to eight main themes. The most critical challenges were: not forming an integrated leadership model, and a shared vision among different HRS stakeholders. Their scope and activities had contradictions, and their role was not clarified in a predetermined big picture. The other challenges were in legislation, priority setting, monitoring and evaluation, networking, and using evidence as a decision support base.Conclusion: Stewardship functions are inappropriately performed, and they are considered the root causes of many other HRS challenges in Iran. Formulating a clear shared vision and formulating the work scope for HRS actors is critical, along with integrating all efforts toward a unified strategy that assists in addressing many challenges of HRS. Developing strategic plans, future-oriented and systematic research, and evaluating the performances. Policymakers and senior managers need to embrace and use evidence, and effective networking and communication mechanisms among stakeholders need to be enhanced. To have an effective HRS, redesigning the processes, regulations, and rules promotes transparency, accountability, being well-organized and systematic.
Construction and optimization of multi-parameter cement strength numerical model based on percolation
Authors: Liu Wei , Wu Xuguang , Wang Yingbin , Ye Zhiwei , Li Pan
Published: April 2022

The prediction of the mechanical properties of different dosages amounts of cement has been a hot topic in various scholars. In addition to water and a small amount of air and pores, cement has unhydrated cementitious material particles and hydration products. It was found that the hydration products CH and C-S-H gel in cement had certain effects on the mechanical properties of cement. In the theory of many porosity and cement mechanical properties, the theory of porosity and cement mechanical properties based on percolation theory can better predict the strength of cement stone. This paper studies the hydration products on cement,a numerical model of multi-parameter cement mechanical properties based on porosity and hydration products was proposed. By using various optimization algorithms to fit and optimize the constructed numerical model, it was found through multiple experiments and comparisons. The lightning search algorithm can achieve a certain effect on the optimized fitting of the constructed mathematical model. The multi-parameter numerical model based on pore percolation constructed in this paper is well fitted. In terms of predicting cement strength, it is superior to the three most cited porosity strength models at home and abroad and the porosity strength model based on percolation theory.
ZD6474 attenuates TGF-β1-induced fibrosis in human tenon fibroblasts and inhibits neovascularization via AKT-mTOR signaling pathway
Authors: Liu Wenting , Chen Yaying , Song Xiangyuan , Xue Yiwen , Zhang Yuyan
Published: April 2022

Purpose
To investigate the anti-fibrotic effect of ZD6474 (a novel inhibitor of VEGF and EGF) in TGF-β1 stimulated human Tenon’s capsule fibroblasts (HTFs) and the anti-angiogenetic role in HUVECs, compared to that of mitomycin C (MMC).
Methods
The effects of ZD6474 on cell proliferation or migration in TGF-β1-stimulated HTFs and HUVECs were determined, using CCK8 or wound healing assay, respectively. The typical markers of fibrosis in TGF-β1-stimuated HTFs were detected, vimentin by immunofluorescence, αSMA and snail by western blot. Tube formation was applied to validate the anti-angiogenesis effect in HUVECs following ZD6474 treatment. Furthermore, phosphorylated AKT and mTOR (p-AKT and p-mTOR) were evaluated, compared to the standardized total AKT and mTOR, using western blot.
Results
There was almost no decreased cell viability in HTFs following ZD6474 (≤ 1 µM/mL) treatment, but MMC (> 50 µg/mL) significantly impaired cell viability. ZD6474 significantly inhibited TGF-β1-stimulated proliferation and migration in HTFs, compared to control group (**P < 0.01). ZD6474 also significantly attenuated the TGF-β1-stimulated expression of vimentin, α-SMA and snail in HTFs. Tube formation was notably interrupted in HUVECs following ZD6474 treatment (**P < 0.01). PAKT and p-mTOR was significantly decreased in response to ZD6474 treatment in TGFβ1 induced HTFs and HUVECs.
Conclusion
ZD6474 exerts anti-proliferation and anti-fibrotic effects in TGF-β1-stimulated HTFs perhaps via regulating AKT-mTOR signaling pathway. ZD6474 also inhibited proliferation, migration and tube formation in HUVECs via the same signaling pathway. We concluded that ZD6474 may be potentially a novel agent in preventing bleb dysfunction following glaucoma filtration surgery (GFS).
Retrospective cohort study of COVID-19 in patients of the Brazilian public health system with SARS-COV-2 Omicron variant infection
Authors: Murari Thiago , Fonseca Larissa , Pereira Hernane , Filho Aloisio , Saba Hugo , Scorza Fulvio , de Almeida Antonio-Carlos , Maciel Ethel , Mendes José , Filho Tarcísio , Badaró Roberto , MACHADO BRUNA , Moret Marcelo
Published: April 2022

Several vaccines against COVID-19 are now available, based on different techniques and made by different laboratories spread around the world. With the roll out of the vaccination process in an advanced stage in many countries, and the reduced hospitalization risk by the Omicron relative to Delta variant infection, despite the higher transmission risk of Omicron, may lead to a misinterpretation of the results, as infection by Omicron is associated with a significant reduction of severe outcomes and shorter hospitalization time than the Delta variant. We compared the in-hospital mortality due to the Omicron (Jan-Mar 2022) with Gamma (Jan 2021) and Delta (Oct-Dec 2021) variants of patients in the Brazilian public health system. This study also discusses the decrease of booster vaccine effectiveness in hospitalized patients due to the Omicron compared with the Delta variant. Without a remodeling of vaccines for new variants, booster doses may be necessary with a shorter time interval
Weight Change, Carcass Characteristic and Economic Benefit of Yearling Hararghe Highland Rams Fed Diet Containing Concentrate Mixtures and Sugarcane Bagasse or Rice Husk Treated with Trichoderma viride and Effective Microorganisms
Authors: Begna Regasa , Urge Mengistu , Negesse Tegene , Animut Getechew
Published: April 2022

A study was conducted to evaluate body weight change, carcass characteristics and economic benefit of Hararghe highland sheep fed biological treated Rice husk (RH) or sugarcane bagasse (SCB) in total mixed diet. Thirty six sheep with initial weight of 18±1.8kg (mean±SD) were used. A randomized complete block design (RCBD) in 2x3 factorial arrangements consisting two feeds (SCB and RH) and three biological treatments (Control, Trichoderma viride (Tv) and effective microorganism (EM)) was employed. The study period lasted for 90 days of fattening. The total mixed diet was fed adlibitum at a rate of 20% refusal. The result indicated that sheep fed diet contained RH as roughage source had significantly (p<0.05) higher carcass weight, dressing percentage, rib eye muscle area, total non carcass fat and total edible offal components than sheep fed SCB diet. Sheep fed diet contained biological treated feed had significantly (p<0.05) higher hot carcass weight and dressing percentage while other parameters were not affected by treatments. There was no significant difference between diets based on roughage based on Tv and EM treated. Profitability analysis indicated that fattening sheep with diet based on RH and biological treated by-products displayed greater profitability than SCB and untreated. It is concluded that fattening of sheep with Rice husk (RH) and sugarcane bagasse treated with Trichoderma viride and effective microorganism (EM) yield more carcass and fetch better profit, but optimum inclusion levels need other investigation particularly for sugarcane bagasse (SCB).
Systematic identification of Pseudomonas based on an internal transcribed spacer (ITS) combined with next-generation sequencing
Authors: Hu Shuqian , Li Xiang , Yin Xin , Li Runmeng , Zhang Ruiyang , Zang Junhao , Liu Yin
Published: April 2022

Background
Pseudomonas species are widely distributed in the human body, animals, plants, soil, fresh water, seawater, etc. Pseudomonas aeruginosa is one of the main pathogens involved in nosocomial infections. It can cause endocarditis, empyema, meningitis, septicaemia and even death. However, the Pseudomonas classification system is currently inadequate and not well established.
Results
In this study, the whole genomes of 103 Pseudomonas strains belonging to 62 species available in GenBank were collected and the specificity of the 16S–23S ribosomal RNA internal transcribed spacer (ITS) sequences was analysed. Secondary structures of ITS transcripts determining where the diversity bases were located were predicted. The alignment results using BLAST indicated that the ITS sequence is specific for most species in the genus. The remaining species were identified by additional frequency analyses based on BLAST results. A double-blind experiment where 200 ITS sequences were randomly selected indicated that this method could identify Pseudomonas species with 100% sensitivity and specificity. In addition, fish samples combined with this method and next-generation sequencing were utilized to identify the proportion of Pseudomonas species in the samples.
Conclusions
The results showed that the ITS-based analytical method enabled accurate classification of Pseudomonas at the species level.
Association between vitamin C and prostate cancer: evidence from meta-analysis of clinical trials and Mendelian randomization
Authors: He Yushi , Yuan Chi , Jian Zhongyu , Jin Xi , Li Hong , Wang Kunjie
Published: April 2022

Background: Prostate cancer ranks the second in the cancer of male patients worldwide. And previous studies gave controversial conclusions on the prostate-cancer-prevention effect of vitamin C. This meta-analysis and Mendelian randomization aimed to investigate the causal association between vitamin C and prostate cancer.Materials and Methods: The meta-analysis included prospective cohort studies and randomized controlled trials (RCT) from multiple databases up to 2021 January to assess association between vitamin C supplementation and prostate cancer. In the two-sample Mendelian randomization (MR) analysis, instrumental variables of plasma vitamin C were-extracted from a large-scale genome wide association study (GWAS) meta-analysis(n·=52,018). Outcome data of prostate cancer were from Prostate Cancer Association Group to Investigate Caner-Associated Alterations in the Genome (PRACTICAL) and FinnGen project with 208,525 participants. Inverse variance weighted, MR-Egger, weighted-median, and weighted mode methods were applied to assess the causal effect of plasma vitamin C on prostate cancer.Results: Four prospective cohorts and one randomized controlled trial with 44,651 participants were included in the meta-analysis. The pooled effect did not demonstrate an insignificant relationship between vitamin C supplementation and prostate cancer incidence (OR 1.03, 95% CI 0.95-1.11, p=0.089). Similarly, the results of MR provided insufficient evidence to support the causal association between plasma vitamin C and prostate cancer both on the data from PRACTICAL (IVW: OR 0.96, 95% CI 0.88-1.05, p=0.399) and FinnGen project (IVW: OR 0.96, 95% CI 0.75-1.24, p=0.767). Conclusions: The findings of meta-analysis and MR analysis provided insufficient evidence that neither vitamin C supplementation nor plasma vitamin C level were associated with prostate cancer.
Identification of four Ferroptosis Gene signatures and Establishment of a predictive model for the overall survival rate of gastric cancer
Authors: Liu Jiang , Tian Hua-kai , Fu Nan-tao , Hu Ce-gui , Zou Fei-long , Zong Zhen , Ning Zhi-kun
Published: April 2022

Background: Gastric cancer (GC) is highly aggressive and recurrent. Ferroptosis is believed to be closely related to the occurrence and development of tumors, but the specific mechanism is still unclear. This study aims to construct a new prognostic model based on ferroptosis-related gene scores to assess the prognosis of GC patients and guide clinical treatment.Materials and Methods: The gene expression information of GC patients with clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between tumor and normal tissue were screened from TCGA dataset, and ferroptosis-related genes were downloaded from the ferroptosis database. The ferroptosis-related DEGs were identified by intersecting the ferroptosis-related genes with DEGs. Univariate Cox and LASSO regression analysis was applied to identify survival-related intersection genes (SRIGs) and 4 hub genes. The TCGA dataset was randomly divided into 2 cohorts in a ratio of 0.7:0.3, the training cohort for construction of signature and the testing cohort for internal validation. The GSE26901 was used for external validation. Receiver operating characteristic (ROC), Kaplan-Meier curve and risk curve of 3 cohorts were plotted to evaluate performance of the signature. Multivariate Cox regression analysis was used to determine independent prognostic factors for gastric cancer, and then a prognostic nomogram was established based on risk score and clinicopathological parameters.Results: A four-gene signature comprising MYB, CHAC1, NOX4 and AFT3 was constructed to predict overall survival of GC. Using the best cut-off value to divide patients into high-risk and low-risk groups, we found that the survival rate of the low-risk group in the training group, test group and external validation group was significantly higher than that of the high-risk group (P<0.05). The area under the ROC curve for 1 year, 3 year, and 5 year were (0.635, 0.666, 0.713), (0.63, 0.681, 0.602) and (0.758, 0.679, 0.677). Both univariate and multivariate Cox regression analysis showed that 4 gene markers are independent prognostic factors for GC. The 1-year, 3-year and 5-year overall survival consistency tests show that the nomogram has good predictability. Immune correlation analysis of high-risk population indicated that tumor progression may be related to the high expression of Macrophages.Conclusion: Our study identified a signature with 4 ferroptosis-related genes and established a reliable prognostic nomogram for predicting the overall survival rate of GC patients. The results may help medical decision-making, and provide a novel reference for predicting the prognosis of GC and even potential molecular targets.
Hyponatraemia in paediatric patients, is it so frequent and so severe?
Authors: Rius-Peris Juan M , Tambe Parag , Chilet-Sáez Marifina , Requena Mariano , Mateo Jorge , Prada Enrique
Published: April 2022

ObjectivesHyponatraemia is the most common electrolyte disturbance in hospitalized children with an incidence of 15-30%. The overall frequency of hyponatraemia and its severity are not well known. The objective of our study was to determine the incidence, severity and associated risk factors of community and hospital acquired hyponatraemia, on a general paediatric ward.Study designPseudonymised admission data was collected for 5550 children admitted to the paediatric ward from June 2012 to December 2019 on plasma sodium and discharge diagnosis with ICD codes. Clinically relevant diagnostic groups were created based on coding diagnosis. Hyponatraemia was classified as mild, moderate and severe; and community acquired (CAH) and hospital acquired (HAH) hyponatraemia. Incidence, severity and risk factors were analysed by logistic regression model.ResultsPlasma sodium levels were available in 3102 out of 5550 admitted children. The incidence of CAH was 15.8% in contrast to 1.4% for HAH. Most of the cases were mild (90.8%) to moderate (8.6%) with only two cases of severe CAH. There were no clinical complications in any of the hyponatraemic children. Age, length of stay and diagnosis at discharge were important factors significantly correlated with CAH.ConclusionsCommunity acquired hyponatraemia is more common than hospital acquired hyponatraemia in clinical practice. Severe cases of both are rare. Children from 2-11 years presenting with infections, cardiovascular disorders and gastrointestinal disorders are at higher risk of developing hyponatraemia with longer hospital stays. Further multicentre studies are needed to ascertain the true incidence, severity and clinical consequences of this electrolyte disturbance.
Lived experience of people on anti-retro viral therapy in the context of covid-19: aphenomenological study
Authors: Derbew Tadele , Ambaw Fentie , Wasihun Yosef
Published: April 2022

Introduction: People living with human immune virus (HIV) are confronting multiple psychosocial and economic issues influenced by the illness. People on anti-retro viral drugs (ART) were at risk for discontinuation of medications during corona viral disease-2019 (COVID-19) pandemic. COVID-19 outbreak made people living with HIV (PLWH) to experience critical challenges and barriers to optimal care. The experience of people living with HIV such as stigma and discrimination, economic problem, psycho social problem before the emergency of COVID-19 was studied but there is lack of understanding on the lived experience of people living with HIV in the context of COVID-19 in Ethiopia particularly in Tach Gayint. This study aimed to explore the lived experience of people on ART in context of COVID-19 in Tach Gayint district. Methods and materials: Phenomenological study design was conducted with 16 study participants from March 12-April 12/2021. Data were collected using in-depth interview using interview guide and digital recorder. The investigator took note in addition to digital record. Interviews were transcribed word for word and translated conceptually. Analysis followed Reading of transcriptions, develop and apply coding, displaying data, data reduction and interpretation. Atlas.ti-7 software was used to facilitate analysis. The quality of data was assured by the principles of credibility, dependability, conformability and transferability. Result: The study explored psychological experience, change in social interaction, and economic experience and ART drug interruption as the main themes including other sub-themes. Most participants perceived the severity of COVID-19 on them. Lack of participation in social activities due to fear of contracting and dying and loss of income were experienced by the participants. This extreme fear pushed some participants to interrupt their daily ART intake especially during lock down period. Personal, familial and community context contributed for these distressing experiences. Conclusion and recommendation: This study reported participants’ psychosocial, economic experiences including ART drug interruptions. It is recommended for the government to design policies and interventions to alleviate their personal, household and community problems which were the caused for the mentioned hostile experiences.
Application of developmental anatomy in laparoscopic complete mesocolic excision for right-sided colon cancer
Authors: Li Kai , Cao Fengyu , He Xiaobo , Zheng Yongbin
Published: April 2022

Development of the midgut is characterized by rapid elongation of the gut and its mesentery, resulting in the formation of the primary intestinal loop, which rotates around an axis formed by the superior mesenteric artery. Eventually, a complex twisted intestinal and mesenteric anatomy is formed by displacement, rotation, and fusion. Therefore, we theoretically believed that the colon and its mesentery should be restored to the simple primitive mesenteric state, and then en bloc resection could be better performed. In the present study, we introduced a surgical technique for complete mesocolic excision (CME) based on the concept of developmental anatomy, which was successfully performed on 65 patients with right-sided colon cancer. At 12 months follow-up, there were no intra-operative or major postoperative major complications, no tumor recurrence, and no deaths within postoperative 30 days. In conclusion, the surgical procedure of CME based on the concept of developmental anatomy is technically safe and feasible for right-sided colon cancer.
Improved animal genetics deliver low emissions development in East Africa’s dairy sector
Authors: Hawkins James , Komarek Adam , Kihoro Esther M , Nicholson Charles F , Omore Amos , Schoneveld George C , Yesuf Gabriel U , Ericksen Polly J , Rufino Mariana
Published: April 2022

Smallholder farm-households produce most of the crop and livestock products consumed in developing countries. Equitable transitions to low emissions food production will depend on policies that promote a reduction of greenhouse gases (GHGs) whilst improving these farmers’ livelihoods. Here, using survey data and simulation modelling, we show that Tanzania’s public programme to reduce import dependence through efficiency gains in the dairy sector increases farmer incomes (+12-20%) whilst reducing GHG emissions consistent with the Nationally Determined Contributions pledge (21-39%). Scenario analysis demonstrates that incrementally higher proportions of improved cattle (Bos taurus crosses) in the herd lead to greater reductions in GHGs over the Baseline, whilst benefitting producers through higher marketable surpluses and household income. As East Africa has the highest population density of indigenous Bos indicus cattle in Africa, genetic gains will be a key lever for reconciling food sovereignty with climate mitigation pledges throughout the region.
Volatile Scents Preference of Crab Spiders (Ebrechtella Tricuspidata) for Host Flowers
Authors: LI ZICHANG , SU QICHEN , ZHAO YAO , YUN YUELI , Peng Yu
Published: April 2022

Chemical signals are important to all living organisms, especially to plants which don’t have vision or mobility. Plant volatiles participate in the competition between plants, herbivores and predators; meanwhile, the tritrophic interactions promote the evolution of plant volatiles. To our knowledge, spiders are common predators in the interactions, but only few studies have begun to investigate what floral volatiles do to spiders. Here, we used Ebrechtella tricuspidata and their common host flowers (tulips) found in our previous field survey to determine the volatile scent preference of spiders for host flowers. Eight main floral volatile scent compounds of tulips were picked out and tested in dual choice behavioural assays. E. tricuspidata showed a significant avoidance of α-pinene and no preference for limonene, β-ocimene, linalool, benzaldehyde, benzyl-alcohol, methyl-salicylate, or 2-phenylethanol. The results illustrate that facultative flower visitor E. tricuspidata is not popular among some kinds of tulip. This probably represents a typical response: facultative flower visitors cannot tolerate all defensive floral volatile scents. Compared with previous studies, we detect that the same floral volatile scent compound has different effects on different spiders, indicating that floral volatile scent compounds attract and reject spiders with specificity and they evolved for different functions and targets. However, this is a preliminary study on the effects of chemical signals on plant-spider interactions, both chemical and physical signals should be considered in future research.