bluuebunny/crossref_metadata_2025 huggingface dataset:
Removing Harvest Residues from Hardwood Stands Affects Tree Growth, Wood Density and Stem Wood Nutrient Concentration in European Beech (Fagus Sylvatica) and Oak (Quercus spp.)
Authors: Roy Sanjoy , Leban Jean-Michel , Zeller Bernd , Van-Der-Heijden Gregory , Reichard Arnaud , Gehin Marie-Christine , Santenois Philippe , Saint-Andre Laurent
Published: August 2021

Background: Increased exportation of harvest residues from forests, to mitigate excessive demand for woody biomass, have reportedly diminished soil mineral resources and may lead to degraded tree nutrition and tree growth. However, as nutrients become less available in the soil, the remobilization of nutrients in biomass tissues (plant internal cycling) helps sustain tree nutrition. Our study aims to quantify the impact of Removing Harvest Residues and Litter (RHRL) during five years on tree growth, wood density and stem wood nutrient concentrations in young beech and oak forest stands.Result: Our study found that, RHRL significantly decreased the tree growth ring width, by 14%, and wood density, by 3%, in beech trees, in the near bark rings. RHRL also significantly reduced the nutrient concentration in the near bark and near pith area of both species. Mg, Na and S were found lower by 44%, 76% and 56%, respectively, in the near bark area of beech trees, and K, Ca, Mg, Na, S and Fe were lower by 20%, 25%, 41%, 48%, 41% and 16%, respectively, in the near bark area of oak trees. K and Mg concentrations decreased more strongly in the near pith area compared to the near bark area suggesting internal translocation of these two elements. Conclusion: In beech trees, wood density proved to be an important factor while quantifying the effect of removing harvest residuals on the tree growth and biomass. Soil nutrient loss intensified the remobilization of nutrients contained in older tree rings (close to the pith) towards newly formed rings (close to bark). In our study, in beech trees, K was found to be the most recycled major nutrient. These results demonstrate the potential of such analysis for providing valuable insight into the effect of RHRL in premature stands on the physiological adaptive strategies of trees and an indication of soil fertility and acidity status.
Development and Assessment of PharmaCheck: An Electronic Screening Tool for the Prevention of Twenty Major Adverse Drug Events
Authors: Skalafouris Christian , Reny Jean-Luc , Stirnemann Jérôme , Grosgurin Olivier , Eggimann Francois , Grauser Damien , Teixeira Daniel , Jermini Megane , Bruggmann Christel , Bonnabry Pascal , Guignard Bertrand
Published: August 2021

Background: Adverse drug events (ADEs) can be prevented by deploying clinical decision support systems (CDSS) that directly assist physicians, via computerized order entry systems, and clinical pharmacists performing medication reviews as part of medical rounds. However, physicians using CDSS are known to be exposed to the alert-fatigue phenomenon. Our study aimed to assess the performance of PharmaCheck—a CDSS to help clinical pharmacists detect high-risk situations with the potential to lead to ADEs—and its impact on clinical pharmacists’ activities.Methods: Twenty clinical rules, divided into four risk classes, were set for the daily screening of high-risk situations in the electronic health records of patients admitted to our General Internal Medicine Department. Alerts to clinical pharmacists encouraged them to telephone prescribers and suggest any necessary treatment adjustments. PharmaCheck’s performance was assessed using the intervention’s positive predictive value (PPV), which characterizes the proportion of interventions for each alert triggered. PharmaCheck’s impact was assessed by considering clinical pharmacists as a filter for ruling out futile alerts and by comparing the final clinical PPV with a pharmacist (the proportion of interventions that led to a change in the medical regimen) to the final clinical PPV without a pharmacist.Results: Over 132 days, 447 alerts were triggered for 383 patients, leading to 90 interventions (overall intervention PPV = 20.1%). By risk class, intervention PPVs made up 26.9% (n = 65/242) of abnormal laboratory value alerts, 3.1% (4/127) of alerts for contraindicated medications or medications to be used with caution, 28.2% (20/71) of drug–drug interaction alerts, and 14.3% (1/7) of inadequate mode of administration alerts. Clinical PPVs reached 71.0% (64/90) when pharmacists filtered alerts and 14% (64/242) if they were not doing it.Conclusion: PharmaCheck enabled clinical pharmacists to improve their traditional processes and broaden their coverage by focusing on 20 high-risk situations. Alert management by pharmacists seemed to be a more effective way of preventing risky situations and alert fatigue than a model addressing alerts to physicians exclusively. Some fine-tuning could enhance PharmaCheck's performance by considering the information quality of triggers, the variability of clinical settings, and the fact that some prescription processes are already highly secured.
Phytoremediation of Contaminated Water by Cadmium (Cd) Using Two Cyanobacteria Species (Anabaena Variabilis and Nostoc Muscorum)
Authors: El-Hameed Mona Mohamed Abd , Abuarab Mohamed , Al-Ansari Nadhir , Mottaleb Shady Abdel , Bakeer Gomaa A. , Gyasi-Agyei Yeboah , Mokhtar Ali
Published: August 2021

Background: Water pollution with heavy metals is a severe dilemma that worries the whole world related to its risk to nature ecosystem and human being health. The main objective is to evaluate the removal efficiency of Cd with various concentrations from contaminated aqueous solution by two Cyanobacteria species (Nostoc muscorum and Anabaena variabilis). For this purpose, a designed laboratory pilot scale was applied using two cyanobacteria species (Nostoc muscorum and Anabaena variabilis), four different initial concentrations (0, 0.5, 1.0 and 2.0 mg L−1) for 21 days. Results: N. muscorum was more efficient than A. variabilis for removing Cd (II), because the optimum value of residual Cd achieved by N. muscorum after 21 days at (0.5 mg L-1) was (0.033 mg L-1), where the removal efficiency was 93.4%, while the residual Cd (II) by A. variabilis under the same conditions was (0.054 mg L-1), and the achieved removal efficiency was 89.13%. Algal growth parameters and Photosynthetic pigments were estimated for both Cyanobacteria species through the incubation period. Conclusions: High Cd concentration had a more toxic impact on algal growth. The outcomes of this study will help to produce treated water that could be reused in agrarian activities.
Improving Remote Sensing-based Estimation of Mangrove Forest Gross Primary Production by Quantifying Environmental Stressors: Sea Surface Temperature, Salinity, and Photosynthetic Active Radiation
Authors: Zheng Yuhan , Takeuchi Wataru
Published: August 2021

Mangrove ecosystems play an important role in global carbon budget, however, the quantitative relationships between environmental drivers and productivity in these forests remain poorly understood. This study presented a remote sensing (RS)-based productivity model to estimate the light use efficiency (LUE) and gross primary production (GPP) of mangrove forests in China. Firstly, LUE model considered the effects of tidal inundation and therefore involved sea surface temperature (SST) and salinity as environmental scalars. Secondly, the downscaling effect of photosynthetic active radiation (PAR) on the mangrove LUE was quantified according to different PAR values. Thirdly, the maximum LUE varied with temperature and was therefore determined based on the response of daytime net ecosystem exchange and PAR at different temperatures. Lastly, GPP was estimated by combining the LUE model with the fraction of absorbed photosynthetically active radiation from Sentinel-2 images. The results showed that the LUE model developed for mangrove forests has higher overall accuracy (RMSE = 0.0051, R2 = 0.64) than the terrestrial model (RMSE = 0.0220, R2 = 0.24). The main environmental stressor for the photosynthesis of mangrove forests in China was PAR. The estimated GPP was, in general, in agreement with the in-situ measurement from the two carbon flux towers. Compared to the MODIS GPP product, the derived GPP had higher accuracy, with RMSE improving from 39.09 to 19.05 g C/m2/8 days in 2012, and from 33.76 to 19.51 g C/m2/8 days in 2015. The spatiotemporal distributions of the mangrove GPP revealed that GPP was most strongly controlled by environmental conditions, especially temperature and PAR, as well as the distribution of mangroves. These results demonstrate the potential of the RS-based productivity model for scaling up GPP in mangrove forests, a key to explore the carbon cycle of mangrove ecosystems at national and global scales.
Eco-friendly based Integrated Management Practice against Root-Knot Nematode, Meloidogyne incognita on Cluster bean (Cyamopsis tetragonoloba L.)
Authors: Nama Chandra Prakash , Baheti B.L.
Published: August 2021

AimThe experiment was carried out during two consecutive Kharif seasons to test the combined efficacy of biochemicals i.e. salicylic acid, ascorbic acid and L-arginine each at 2 % w/w as seed treatment and botanicals viz. neem, lantana and parthenium leaves powder each at 5 g per plant for the management of root-knot nematode, Meloidogyne incognita infecting cluster bean..Method All treatments applied as soil application at the time of sowing. Before sowing observation on initial nematode population/100 cc soil and at the termination of experiment number of galls/plant, number of egg masses/plant, number of eggs and larvae/egg mass, final nematode population/100 cc soil and yield (q/ha) were recorded. ResultAmong different combinations, minimum nematode population were observed with ascorbic acid at 2 per cent w/w + neem leaves powder at 5 g per plant followed by ascorbic acid at 2 per cent + lantana leaves powder at 5 g per plant and salicylic acid at 2 per cent + neem leaves powder at 5 g per plant.Conclusion: Results of experiment showed that application of biochemicals along with botanicals significantly reduced galls per plant as compared to untreated check.
Chondroitin Sulphate and Gas Foaming Concurrently Improve Articular Cartilage Regeneration in Electrospun Poly(L-lactide-co-ε-caprolactone)/Silk Fibroin Based Scaffolds
Authors: Chen Yujie , Xu Wei , Shafiq Muhammad , Song Daiying , Xie Xianrui , Yuan Zhengchao , Newehy Mohamed EL , Hamshary Hany EL , Morsi Yosry , Liu Yu , Mo Xiumei
Published: August 2021

Degenerated cartilage tissues remain a burgeoning issue to be tackled, while bioactive engineering products available for optimal cartilage regeneration are scarce. In the present study, two-dimensional (2DS) poly(L-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF)-based scaffolds were fabricated by conjugate electrospinning method, and then cross-linked with chondroitin sulfate (CS) to further enhance their mechanical and biological performance. Afterwards, three-dimensional PLCL/SF scaffolds (3DS) and CS-crosslinked three-dimensional scaffolds (3DCSS) with tailored size were successfully fabricated by in situ gas foaming in a confined mold and subsequently freeze-dried. Gas-foamed scaffolds exhibited high porosity, rapid water absorption, and stable mechanical properties. While all of the scaffolds exhibited excellent cytocompatibility in vitro; 3DCSS showed better cell seeding efficiency and chondro-protective effect as compared to the other scaffolds. Histological analysis of chondrocytes-seeded constructs after cultivation for up to 6 weeks in vitro also confirmed that 3DCSS scaffolds supported the formation of cartilage-like tissues along with the more secretion of cartilage-specific extracellular matrix than that of the other groups. The reparative potential of 3DCSS was further evaluated in an articular cartilage defect model in rabbits, which exhibited a well-integrated boundary and attenuated inflammation demonstrating less expression of pro-inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Taken together, the engineered biomimetic 3DCSS may provide a well-suited therapeutic option for cartilage tissue regeneration applications.
Endoplasmic Reticulum Stress-related Classification for Prognosis Prediction in Hepatocellular Carcinoma
Authors: Zhang Genhao
Published: August 2021

Background: Cancer cells under ER stress are common in hepatocellular carcinoma (HCC) and ER stress is strongly associated with poor prognosis. The aim of this study was to discover credible biomarkers for predicting prognosis of HCC based on ER stress-related genes (ERSRGs). Methods: Univariate Cox regression was performed to calculate the association between ERSRGs and survival outcomes of HCC patients in TCGA. Then LASSO-Cox regression strategy and stepwise Cox regression examination were performed to investigate the quality and establish the prognostic characteristics associated with prognosis. Finally, the model was subsequently validated in two additional independent HCC cohorts.Results: A novel seven-gene prognostic risk model based on ERSRGs was constructed and exhibited superior accuracy in forecasting the survival outcomes and 1-, 2-, 3- year survival rate of HCC patients. qRT-PCR was performed to validate the prognostic risk model in an independent clinical cohort containing 59 HCC patients and the results revealed that this signature had a good prognostic performance. Moreover, we found ER stress could affect the immune microenvironment in HCC and immune checkpoint inhibitors (ICIs) treatment was more effective for patients in high-risk subgroup. In addition, we identified 103 tumor-sensitive drugs in the CellMiner database that may be available for the treatment of HCC patients targeting ER stress and constructed a nomogram combining ER stress-related feature, TNM stage, age and gender. Conclusions: Our seven genetic risk model associated with ER stress can accurately predict survival outcome in HCC patients and facilitate the selection of the best individualized treatment targeting ER stress.
Revised Morphological Characteristics of Species of Two Ostracod Genera Loxoconcha Sars, 1866 (Loxoconchidae) and Xestoleberis Sars, 1866 (Xestoleberididae)
Authors: Le Doan Dung
Published: August 2021

Total 23 species of the genus Loxoconcha and 21 species of the genus Xestoleberis were presented in this study. A scanning electron microscope for observing muscle scars of the carapaces, and a stereoscopic microscope for dissecting, observing and sketching the appendages were used. The results show that most species of the genus Loxoconcha consist of four adductor scars to arrange in a curved sub-vertical row and concave anteriorly, except L. pulchra carrying five, in which the top one is divided into two. The frontal scars with C-shape, opening anteriorly are presented in most of Loxoconcha species, however, the frontal scar with bean-shape or oval-shape is discovered in five species of L. japonica group. Most of L. kosugii bear the frontal scar with C-shape, but the frontal scar with Y-shape is found in several individuals. This phenemenon shows the close phylogeny between the genus Loxoconcha and Palmoconcha. About the genus Xestoleberis, chaetotaxy of setae on all appendages, except setae of exopodite on the maxillula is a typical character of this genus. The published fossil records and the tendencies of change in the number of setae on the maxillula and mandible among three phylogenetic groups suggest that Group A or B is an ancestor of the genus Xestoleberis, and Group C is a derived group.
Evaluation of Prophage Gene Revealed Population Variation of ‘Candidatus Liberibacter Asiaticus’: Bacterial Pathogen of Citrus Huanglongbing (HLB) in Northern Thailand
Authors: Kongjak Jutamas , Akarapisan Angsana
Published: August 2021

The authors have requested that this preprint be removed from Research Square.
Altered static and dynamic functional connectivity in subthreshold bulimia nervosa: A resting-state functional magnetic resonance imaging(fMRI) study
Authors: Luo Lin , Luo Yijun , Chen Ximei , Xiao Mingyue , Bian Ziming , Leng Xuechen , Li Wei , Wang Junjie , Yang Yue , Chen Hong
Published: August 2021

Bulimia nervosa (BN) is one of the most serious eating disorders (EDs) associated with long-term significant impairment to both physical and mental quality of life. Subthreshold BN emphasize that individuals reported some extent bulimic symptoms, even those individuals who did not fully meet the diagnostic criteria endure elevated levels of impulsivity and higher likelihood of self-harm. Therefore, the current study aimed to identify potential neurobiological signatures of high-risk individuals with BN symptoms. We used functional magnetic resonance imaging (fMRI) to investigate the differences between a subthreshold BN group (sub-BN, n = 61) and a control group (n = 51) in terms of degree centrality (DC), with the secondary analysis of the connectivity in these ROIs showing differences in both static functional connectivity (sFC) and dynamic functional connectivity (dFC) with age, sex, and framewise displacement (FD) as covariates of no interest (p < 0.05, GRF corrected). The sub-BN group exhibited significantly increased DC in the left middle frontal gyrus (MFG) and the orbital frontal gyrus, increased MFG‒superior occipital gyrus connectivity, MFG‒middle occipital gyrus connectivity and MFG‒triangular part of the inferior frontal gyrus (IFGtriang) connectivity, and decreased variability in MFG‒anterior cingulate cortex connectivity. Furthermore, in the sub-BN group, a positive correlation was observed between self-reported BN symptoms and MFG‒IFGtriang connectivity. These findings implicated in reward value processing, cognitive control, and self-referential processing in individuals with BN symptoms, which provided important insights into understanding the pathology of BN.
Polygenic prediction of lipid traits in sub-Saharan Africans
Authors: Fatumo Segun , Kamiza Abram , Toure Sounkou , Vujkovic Marijana , Machipisa Tafadzwa , Soremekun Opeyemi , Kintu Christopher , Corpas Manuel , Pirie Fraser , Young Elizabeth , Gill Dipender , Sandhu Manjinder , Kaleebu Pontiano , Nyirenda Moffat , Motala Ayesha , Chikowore Tinashe
Published: August 2021

Polygenic risk scores (PRS) can enhance risk stratification and are useful for precision medicine interventions. Here we show that African American Genome-wide Association Study (GWAS) derived PRS enhance prediction of lipid traits in Sub-Saharan Africans. Our PRS prediction varied greatly between South African Zulus (LDL-C, R2 = 8.49%) and Ugandans (LDL-C, R2= 0.043%), potentially attributable to environmental factors. Moreover, the PRS shown here had a higher discriminatory ability (AUC = 74.6%) than conventional risk factors (AUC= 67.8%) to identify extreme phenotypes. This work highlights the utility of PRS derived from relevant ethnic groups for identifying high-risk cases missed by conventional clinical factors.
Husband/Wife Joint AB Blood Group is Associated With Clinical Outcomes of IVF/ICSI Treatment in Chinese Women
Authors: Bao Xiao , Zhao Feifei , Shi Hao , Bu Zhiqin , Lang Yuling , Sun Ying-Pu
Published: August 2021

Background: A number of publications have been studied the relation between blood group and female infertility including ovarian reserve, recurrent miscarriage and live birth, there is a lack of literature investigating joint wife/husband ABO blood type in large cohort. The aim of this study was to investigate the association between couple combinations for ABO blood groups and ART outcomes in patients undergoing IVF/ICSI.Methods: This retrospective cohort study included 30,717 couples underwent IVF cycles between 2010 and 2019. Clinical outcomes of IVF treatment was the primary outcome. History of spontaneous miscarriage, embryo quality, and birth sex, weights, defects rate were also studied. Multivariable logistic regression was used to examine the association. Odds ratios (OR) with 95% confidence intervals (CI) for each outcome were estimated.Results: There was no difference in the baseline demographics between the blood type groups. There was a statistically significantly positive association between the combination of female blood type AB and male blood type AB with biochemical pregnancy, clinical pregnancy, and live birth rate (OR 1.36; 95% CI, 1.05-1.78; P 0.02 and OR 1.31; 95% CI, 1.03-1.68; P 0.031 and OR 1.28; 95% CI, 1.01-1.63; P 0.041 respectively). No statistically significant difference was observed between joint wife/husband ABO blood types and high-quality embryo rate, early abortion rate, birth sex, birth weights and birth defects rate.Conclusions: Our findings suggest that husband/wife mating AB blood type may increase the success rate of IVF/ICSI cycles.
Modeling oxidative injury response in human kidney organoids
Authors: Przepiorski Aneta , Vanichapol Thitinee , Espiritu Eugenel B. , Crunk Amanda E. , Parasky Emily , McDaniels Michael D. , Emlet Dave R. , Salisbury Ryan , Happ Cassandra L. , Vernetti Lawrence A. , MacDonald Matthew L. , Kellum John A. , Kleyman Thomas R. , Baty Catherine J. , Davidson Alan J. , Hukriede Neil A.
Published: August 2021

BackgroundPersistent acute kidney injury (AKI) leads to tubular atrophy, kidney fibrosis, and, if severe enough, chronic kidney disease (CKD). A common feature of AKI is the generation of excessive reactive oxygen species (ROS) which damage cells and induce inflammation. MethodsHuman kidney organoids were treated with hemin, an iron-containing porphyrin derived from lysed red blood cells, that generates ROS in disease settings such as rhabdomyolysis, sepsis and ischemia reperfusion leading to AKI. In addition, we developed an induced pluripotent stem cell line expressing the biosensor, CytochromeC-GFP (CytoC-GFP), which provides a real-time readout of mitochondrial morphology, health, and early apoptotic events. ResultsWe found that hemin-treated kidney organoids show oxidative damage, increased expression of injury markers, impaired functionality of organic anion and cation transport and undergo fibrosis. Tubule injury could be detected in live CytoC-GFP organoids by cytoplasmic localization of fluorescence. Finally, we show that 4-(phenylthio)butanoic acid, an HDAC inhibitor with anti-fibrotic effects in vivo , reduces hemin-induced human kidney organoid fibrosis. ConclusionTogether this work establishes a hemin-induced model of kidney organoid injury and fibrosis as a new model to study renal repair and a human platform for developing AKI therapeutics.
Synthesis of ZrO2-Al2O3 Composite Beads by Wet Titration Technology
Authors: Peng Dasong , Wang Xiaodong , yanchao Ren
Published: August 2021

In this work, based on the wet titration technology, an innovative method to prepare the ZrO2-Al2O3 composite beads which can greatly improve the bead properties is proposed. Using this process, the ZrO2-Al2O3 composite beads samples with different proportions of alumina component were prepared and tested. The bulk density test results show that the new method can prepare the beads with high compactness and without containing pores. The hardness test results show that the hardness of the composite beads is higher than zirconia beads without adding alumina. The SEM analyses show that the average grain size of the composite beads is about 180 nm, much smaller than the beads prepared by conventional rolling process. The XRD results show that there is no monoclinic phase in the composite beads after sintering at 1250 ℃. The EDS analyses show that the aluminum element exists in composite beads and the alumina grains are evenly distributed. Furthermore, the sintering temperature using this new process can achieve low-temperature sintering which is about 1250 ℃ much lower than the sintering temperature of conventional rolling process.
IMPARTER, Phase 1 of an intervention to improve patients’ understanding of gene expression profiling tests in breast cancer
Authors: Fallowfield Lesley Jean , Farewell Daniel , Jones Hywel , May Shirley Lesley , Catt Susan Lesley , Starkings Rachel Lesley , Jenkins Valerie Lesley
Published: August 2021

Purpose
To compare participants’ knowledge about Gene Expression Profiling (GEP) tests and recurrence risks after reading an information leaflet with that following viewing of an information film.
Methods
Using a randomised cross-over design, at time-point one (T1) women aged 45–75 years without breast cancer, either read leaflets or watched information films about Oncotype DX or Prosigna tests. Participants answered nine questions assessing knowledge, (maximum score 18). Next day information in the opposite modality was provided and knowledge re-assessed. Additional questions probed which format was easiest to understand, participants’ preferences for film or leaflet and their reasons for these.
Results
120 women participated (60 received OncotypeDX films and leaflets; 60 the Prosigna versions). T1 mean knowledge scores were higher following film viewing (13.37) compared with that after reading leaflets (9.25) (mean difference 4.1; p < 0.0001; 95% CI 3.2, 5.0). When participants read leaflets first and subsequently viewed films, all increased their scores (mean + 6.08, from T1 of 9.25, p < 0.0001; 95% CI 5.44, 6.72). When films were viewed first, followed by leaflets, (36/60, 60%) participants’ scores declined (mean-1.55 from T1 of 13.37, p < 0.001; 95% CI -2.32, -0.78). A majority of participants expressed preferences for the films (88/120, 73.3%) irrespective as to whether they described OncotypeDX or Prosigna. Reasons included the clarity, ease of understanding, visual material and reassuring voice-over.
Conclusion
Discussions between oncologists and patients about recurrence risk results can be challenging. Information leaflets may aid understanding but often employ complex language. Information films significantly improved knowledge and were preferred by participants.
Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Role of Renin-Angiotensin System Inhibitors in Bevacizumab -induced Hypertension
Authors: Ren Tianshu , Jia Hui , Wu Qiong , Zhang Yan , Ma Qun , Yao Dong , Gao Xudong , Xie Danni , Xu Zihua , Zhang Yingshi , Zhao Chun Qing
Published: August 2021

Bevacizumab (Bev) is a humanized vascular endothelial growth factor monoclonal antibody that is used with chemotherapeutic drugs for the treatment of metastatic colorectal cancer (mCRC). Bev-induced hypertension (HT) is the most common adverse reaction during clinical practice. However, at present, appropriate antihypertensive agents for Bev-induced HT are unavailable. In this study, retrospective analysis of clinical data from mCRC patients who received renin-angiotensin system inhibitors (RASIs) showed significant survival benefits of overall survival (OS) and progression-free survival (PFS) over patients who received calcium channel blockers (CCBs) and patients who received no antihypertensive drug. An experiment in HCT116 colon cancer cell xenografts in mice confirmed that combined treatment with Bev and lisinopril (Lis), a RASI, synergistically inhibited subcutaneous tumor growth and enhanced the concentration of 5-fluorouracil (5-Fu) in tumor tissues. Our results showed that the addition of Lis did not interfere with the vascular normalization effect promoted by Bev, but also inhibited collagen and hyaluronic acid (HA) deposition and significantly downregulated the expression of TGF-β1 and downstream SMAD signaling components which were enhanced by Bev, ultimately remodeling primary ECM components. In conclusion, RASIs might be the optimal choice for the treatment of Bev-induced HT in mCRC patients.
The Clinicopathological Features of BRG1-deficient Non-small Cell Lung Cancer and Its Response to Immunotherapy: A Single-center Retrospective Study
Authors: Chen Xiaoyan , Zhang Jing , Zhao Runze , Xu Haimin , Dong Lei
Published: August 2021

PurposeBRG1-deficient NSCLCs have been more intriguing recently for its highly aggressive clinical behavior and no effective therapies. This study characterized the clinical and pathological features of BRG1-deficient NSCLCs and investigated their response to immunotherapy.MethodsForty-seven cases with BRG1-deficient NSCLC were included. Immunohistochemical markers such as CK7, TTF-1, NapsinA, P40, HepPar-1, Ki-67, BRM, ARID1A and ARID1B were stained. Meanwhile, the PD-L1 expression level, overall survival, progression-free survival and disease control rate of patients received immunotherapy were evaluated.ResultsThis study revealed that: (1) Patients with BRG1-deficient NSCLC have a male predominance(89.4%), smoker enrichment(76.6%) and poor prognosis(median OS: 7.0 months for advanced stage). (2) Histologically, BRG1-deficient NSCLCs presented significant morphological diversity and no lepidic pattern. Inflammatory infiltration and tumor necrosis was a prominent feature. Immunohistochemical analyses showed a distinctive uniform immunophenotype (TTF-1-/NapsinA-/CK7+) in 60.9% (28/46) of cases and HepPar-1 positive in 46.5% (20/43) of cases. BRM loss or significant reduction coexisted in 11.8% (4/34) of cases. No case (0/37) showed loss of ARID1A or ARID1B. (3) For twenty-nine patients with advanced stage, eight patients had received immunotherapy and 4 cases achieved a sustainable clinical response with the disease control rate of 50%. ICIs treated patients had better OS than those who received non-ICIs treatment settings (median OS, 27.0m versus 6.0m, p=0.02). Moreover, patients received ICIs have a median PFS of 17.0 months, while, median PFS on platinum doublet chemotherapy were only 6.0 months(p=0.04). Conclusion﻿BRG1-deficient NSCLC showed diverse histopathological patterns and a unique immunohistochemical phenotype. ICIs–based immunotherapy was a beneficial therapy for BRG1- deficient NSCLC.
Manufacturing Parameters Optimization and Modeling of PxGyEz Hybrid Composite for High Flexural Strength Using Taguchi Robust Experimental Design Technique and General Regression Analysis
Authors: Samuel Bassey Okon
Published: August 2021

With the continuous need for sustainable, environmentally friendly, and low-cost systems, processes, and materials, natural fibers have been a major topic of discussion in the materials science community as it has increasingly found acceptance in material development as an alternative to synthetic fibers due to environmental concerns. Although many studies have been carried out in this regard, the optimal flexural performance of pineapple leaf fiber/synthetic fiber hybrid reinforced composite has not been studied even with its promising application in aviation, health, and fitness, marine, etc. In this study, a Pineapple Leaf fiber (PALF)/Glass fiber Epoxy hybrid composite PxGyEz (with x, y, and z representing the volume fraction of pineapple leaf fiber, the volume fraction of glass fiber, and fiber length respectively) was developed and its flexural properties optimized and modeled with regards to the variable manufacturing parameters of x, y, and z respectively. For the quality characteristics (flexural strength) investigated, the Minitab®19 software was used to analyze the Taguchi robust experiment design technique on a higher the better basis. The optimum combination of the control factors was found at x = 20%, y = 20%, and z = 25mm. The optimized composite P20G20E25 possessed a flexural strength of 144.4994MPa which was only a 7.17% deviation from the predicted optimum flexural strength. Analysis of variance showed that the PALF had the highest contribution of 23.97% to the flexural strength of the PxGyEz, glass fiber 7.13%, and fiber length 12.79%. SEM Images of the PALF, glass fiber, and the fractured surface of the optimized material P20G20E25 revealed the surface structure which explained their different contribution to the flexural strength of the materials. An equation for the prediction of the flexural properties of PxGyEz was derived from the regression model and it had an approximately 77.57% agreement with experimentation.
Adenine Base-Editing-Mediated Exon Skipping Induces Gene Knockout in Cultured Pig Cells
Authors: ZHU XIANGXING , Pan Jia-sheng , Lin Tao , Yang Ye-cheng , Huang Qiu-yan , Yang Shuai-peng , Qu Zi-xiao , Lin Zi-sheng , Wen Jian-cong , Yan Ai-fen , Feng Juan , Liu Lian , Zhang Xiao-li , Lu Jia-hong , Tang Dong-sheng
Published: August 2021

Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9, Adenine base editor (ABE) convert single A·T pairs to G·C pairs in the genome without generating DNA double-strand breaks, and this method has higher accuracy and biosafety in pig genetic modification. However, the application of ABE in pig gene knockout is limited by protospacer-adjacent motif (PAM) sequences and the base-editing window. Alternative mRNA splicing is an important mechanism underlying the formation of proteins with diverse functions in eukaryotes. Spliceosome recognizes the conservative sequences of splice donors and acceptors in a precursor mRNA. Mutations in these conservative sequences induce exon skipping, leading to proteins with novel functions or to gene inactivation due to frameshift mutations. In this study, adenine base-editing-mediated exon skipping was used to expand the application of ABE in the generation of gene knockout pigs. We first constructed a modified “all-in-one” ABE vector suitable for porcine somatic cell transfection that contained an ABE for single-base editing and an sgRNA expression cassette. The “all-in-one” ABE vector induced efficient sgRNA-dependent A-to-G conversions in porcine cells during single base-editing of multiple endogenous gene loci. Subsequently, an ABE system was designed for single adenine editing of the conservative splice acceptor site (AG sequence at the 3’ end of the intron 5) and splice donor site (GT sequence at the 5’ end of the intron 6) in the porcine gene GHR; this method achieved highly efficient A-to-G conversion at the cellular level. Then, porcine single-cell colonies carrying a biallelic A-to-G conversion in the splice acceptor site in the intron 5 of GHR were generated. RT-PCR indicated exon 6 skipped at the mRNA level. Western blotting revealed GHR protein loss, and gene sequencing showed no sgRNA-dependent off-target effects. These results demonstrate accurate adenine base-editing-mediated exon skipping and gene knockout in porcine cells. This is the first proof-of-concept study of adenine base-editing-mediated exon skipping for gene regulation in pigs, and this work provides a new strategy for accurate and safe genetic modification of pigs for agricultural and medical applications.
Intravenous Immunoglobulin Suppresses Chemotherapy-induced Peripheral Neurotoxicity via Macrophage Modulation in Rats and Mice
Authors: Tanaka Jun , Kajii Masahiko
Published: August 2021

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a serious adverse effect that leads to treatment discontinuation by patients receiving anticancer therapy. Treatment discontinuation is a serious and life-threatening problem for patients with cancer; hence, there is a need for drugs that suppress the induction of CIPN by anticancer drugs. Intravenous immunoglobulin (IVIg) reportedly suppresses bortezomib-induced CIPN in a rat model. Here, using rodent models, we showed that IVIg can also suppress peripheral neurotoxicity induced by anticancer drugs other than bortezomib. Furthermore, the suppressive effect of IVIg disappeared when macrophages were depleted. These findings indicate two novel independent possibilities of alleviating CIPN using IVIg. First, CIPN can be controlled by macrophage modulation. Second, IVIg directly combined with anti-cancer drugs can avoid restrictions on the use of anti-cancer drugs due to CIPN inductions. However, further research is necessary for the bench-to-bedside translation of these novel applications of IVIg. Our findings lay a strong foundation for research on IVIg therapeutics.
Antimicrobial Sensitivity Profile of Bacteria Isolated in Babitonga Bay
Authors: Vecchia Maria Tereza Dalla , Schneider Andréa , de França Paulo Henrique Condeixa , Gern Regina Maria Miranda
Published: August 2021

Antimicrobial resistance is one of the main and growing public health concerns. However, the analysis of the expansion of this phenomenon in the environment is limited. Thus, the objective of this work was to determine the antimicrobial susceptibility profile of bacteria isolated from Baía Babitonga. Isolation and identification of microorganisms were carried out from the mangrove sediment sample, collected at two sampling points in Baía Babitonga. Microbial identification analyzes demonstrated the presence of Gram-negative microorganisms, for which the antimicrobial susceptibility profile analysis showed the presence of resistance to Aztreonam, Ciprofloxacin, Cefuroxim, Nitrofurantoin, Meropenem, Tetracyclin, Cefotaxime, and Ceftazidime. For the identified Gram-positive microorganisms, the presence of resistance to Ampicillin and Clindamycin was evidenced. The genotypic investigation showed that the resistances found were not caused by the researched genes (blaSHV, blaCTX-M, blaOXA-48-like, blaKPC, blaNDM-1, blaVIM e blaIMP).
Automated Machine Learning: a case study of genomic “image-based” prediction in maize hybrids
Authors: Galli Giovanni , Sabadin Felipe , Yassue Rafael Massahiro , de Souza Cassia Galves , Carvalho Humberto Fanelli , Fritsche-Neto Roberto
Published: August 2021

Machine learning methods such as Multilayer perceptrons (MLP) and Convolutional Neural Networks (CNN) have emerged as promising methods for genomic prediction (GP). In this sense, we assess the performance of MLP and CNN on regression and classification tasks in a case study with maize hybrids. The genomic information was provided to the MLP as a relationship matrix and to the CNN as “genomic images”. In the regression task, the machine learning models were compared along with GBLUP. Under the classification task, MLP and CNN were compared. In this case, the traits (plant height and grain yield) were discretized in such a way to create balanced (moderate selection intensity) and unbalanced (extreme selection intensity) datasets for further evaluations. An automatic hyperparameter search for MLP and CNN was performed, and the best models were reported. For both task types, several metrics were calculated under a validation scheme to assess the effect of the prediction method and other variables. Overall, MLP and CNN presented competitive results to GBLUP but improved a little using only the additive genomic layer. It is expected that the average effect of allele substitution is mostly linear. Nevertheless, the methodology’s potential for GP is unprecedented because we can create “multispectral genome images,” including other effects and layers of data, such as dominance, epistasis, g × e, transcriptome, and so on, capturing linear and non-linear effects and boosting prediction accuracies. Hence, we bring new insights on automated machine learning for genomic prediction and its implications to plant breeding.
Erucin Inhibits Osteoclast Formation via Suppressing Cell-cell Fusion Molecule DC-STAMP Without Influencing Mineralization by Osteoblasts
Authors: Takagi Tomohiro , Inoue Hirofumi , Fujii Shungo , Takahashi Nobuyuki , Uehara Mariko
Published: August 2021

Objective: Erucin (ERN), an isothiocyanate, is derived from the vegetable arugula. Although ERN has antitumor and antioxidant activity, the effect of ERN on osteoclast and osteoblast differentiation is not well documented. In this study, we evaluated the effects of ERN on osteoclast and osteoblast differentiation in vitro. Results: ERN significantly reduced the formation of 1α,25(OH)2D3-induced tartrate-resistant acid phosphatase (TRAP)-positive cells at non-cytotoxic concentrations. Furthermore, ERN downregulated the mRNA expression of osteoclast-associated genes, such as nuclear factor of activated T cells cytoplasmic-1, TRAP, and cathepsin K. In addition, ERN suppressed dendritic cell specific transmembrane protein (DC-STAMP), which encodes cell-cell fusion. However, ERN did not affect mineralization by osteoblasts. Thus, our data suggest that ERN may attenuate osteoclastic bone resorption by inhibiting multinucleation of mononuclear pre-osteoclasts and by suppressing mRNA expression of DC-STAMP in bone marrow cells without influencing mineralization by osteoblasts.
Fatigue is associated with physical inactivity in people with multiple sclerosis despite different environmental backgrounds: merging and comparing cohorts from Turkey and Israel
Authors: Ozdagar Asiye Tuba , Kahraman Turhan , Ozakbas Serkan , Achiron Anat , Kalron Alon
Published: August 2021

Background Examining physical activity in people with multiple sclerosis (PwMS) from different environmental backgrounds might increase understanding and awareness of inactivity in PwMS.Objectives To compare the level of physical activity in PwMS in Israel and Turkey and to examine the relationship between the level of physical activity with common disease-related symptoms and demographical characteristics of PwMS. Methods Cross-sectional data collected by two centers were combined. The physical activity level was determined by the Godin Leisure-Time Exercise Questionnaire, and subsequently, classified into one of three subgroups: "active", "moderately active" and "insufficiently active". Logistic regressions determined the risks of insufficiently active PwMS, according to age, gender, body mass index, disability, impact of walking impairment, disease duration, type of MS and perceived fatigue. The analysis of variance test determined the differences between countries in terms of outcome variables.Results The study comprised 458 patients from Israel and 575 from Turkey; 68.2% Turkish PwMS were classified as insufficiently active compared with 52.0% of Israeli PwMS. The percentage of insufficiently active PwMS was significantly higher in those categorized as fatigued compared to non-fatigued in the total cohort (72.4% vs. 51.9%, p<0.001) and in each country separately. Based on the regression analysis, fatigue was the main factor associated with the insufficiently physically active group; odds ratio=1.968. Interpretation PwMS with increased fatigue tend to be physically inactive compared with the non-fatigued. This observation is supported by the merged data collected from two countries, Turkey and Israel, representing PwMS from different environmental backgrounds.
Association of extracranial carotid artery stenosis in ischemic stroke in a Sri Lankan cohort of patients - An analytical cross-sectional study
Authors: Rajapakshe Ishani , Wijesundara Devasmitha , Chandrakumara Amila , Senanayake Bimsara
Published: August 2021

Background and Objectives

: The burden of stroke in Sri Lanka is on the increase with the current demographic transition toward an ageing population [1]. However, the association of symptomatic extracranial carotid artery stenosis (CAS) in ischemic stroke has not been prospectively evaluated in a Sri Lankan cohort of patients. Globally population-based studies have estimated about 15% of ischemic strokes are caused by large vessel occlusions. It is commonly believed that the prevalence of significant extracranial CAS is low in Sri Lanka compared to western populations [2, 3]. The purpose of the study is to systematically analyses and assess this long held notion and to search for other associated causative factors.
Methods

The study population comprised 164 acute ischemic stroke patients admitted to the National hospital of Sri Lanka over a period of 3 months. Carotid artery duplex scans were done by a single well-trained operator within 2 weeks of presentation and degree of CAS was classified as low (< 50%), moderate (50–69%), severe (> 70%) and complete occlusion according to NASCET criteria. Factors associated with CAS were identified by stepwise multiple logistic regression analysis.
Results

Out of 164 ischemic stroke patients 104 (63.4%) were male and 60 (36.6%) were female. The mean age of stroke patients was 62.2+- 14.21 years. 139 (84.8%) had low grade stenosis, 10 (6.1%) had moderate stenosis, 7 (4.2%) had severe stenosis and 8 (4.9%) had complete stenosis of carotid artery. Older age and presence of previous TIAs were significantly associated with CAS. Gender, hypertension, diabetes mellitus, hypercholesterolemia, IHD, previous stroke, previous TIA, previous use of antiplatelets, family history of stroke, previous use of statins and presence of carotid bruit were not significantly associated.
Conclusion

Extracranial carotid artery occlusion previously considered a rare cause of ischemic stroke in Sri Lanka was found to be having a prevalence similar to western populations in this study with over 15% having significant stenosis. Hence, we emphasize that early carotid doppler studies must be performed in all ischemic strokes at least within two weeks and necessary interventions carried out where it is deemed necessary.
What works to improve school lunch nutritional quality - legislation or self-audit? Medium-term results from Sweden
Authors: Patterson Emma , Andersson Filip , Elinder Liselotte Schäfer
Published: August 2021

BackgroundPoor monitoring and evaluation leads to a lack of evidence regarding what works in terms of improving school meal quality. Sweden has a long-standing policy of universal free school meals but updated legislation regarding nutritional quality came into effect in 2011. To coincide with this, we built a fully automated web-based self-audit tool for schools, called School Food Sweden, in order to i) establish a national database on overall meal quality, covering six domains, and ii) help schools and municipalities improve, based on the implementation strategy of audit and feedback. We have previously examined the pre- and post-legislation period. In this paper we describe changes in one domain – nutritional quality – in the years since the new legislation and examine if repeated use of the tool was associated with improvements.MethodsPrimary schools in Sweden self-selected to use the tool between March 2012 and July 2019 and audited a four-week lunch menu. Date of audit, number of audits per school (1-9), how often schools accessed their feedback (% of times) and school characteristics were noted. Factors associated with meeting nutritional criteria were examined using variance weighted least squares regression and logistic regression, using both repeated cross-sectional and longitudinal design.ResultsAlmost half of all ca 4800 primary schools in Sweden signed up to the tool. Nutritional quality was audited by 1500 schools at least once. Repeated cross-sectional analyses showed the proportion of all schools meeting the criteria increased significantly between 2012/13 and 2018/19 (from 11% to 34%). For all schools, each extra audit completed increased the odds of meeting nutritional criteria by 1.30 (CI 1.20-1.41), controlling for region and time since the introduction of legislation. In a longitudinal analysis (schools with repeat audits, n=774), both number of audits and the frequency of accessing previous feedback reports were predictors of meeting the nutritional criteria (OR 2.02, CI 1.23-3.31), even after adjusting for time since the introduction of legislation and number of days since the previous audit.ConclusionsBoth legislation and self-audit with automatic feedback appear effective in helping schools to improve school meal quality. Self-audit may be an essential complement to legislation, or a promising alternative in settings where regulation is not an option.
HADONAH IBU NON-MUSLIM MENURUT AL-NAWAWI DAN ABU ZAHROH PERSPEKTIF SOSIOLOGI PENGETAHUAN
Authors: Anam Muhammad Mufti
Published: August 2021

ABSTRACTJurisprudence emerges from the dialectic of a faqih and his intellectual social environment. Hadonah by a non-Muslim mother according to al-Nawawi is not permitted because of the reasons for the maslahah and the benefits of Islam over other religions. This jurisprudence is influenced by the background of al-Nawawi who is a hadith scholar and a linguist. While Abu Zahroh tends to allow non-Muslim mothers to breastfeed Muslim children because a mother loves children more than a father, even though there are some exceptions. This thought was due to Abu Zahroh's social and intellectual background who tended to study jurisprudence across schools and studied positive law, philosophy, and non-Islam religion.Keywords: Hadonah, non-Muslim, al nawawi, abuzahroh, sociology of knowledge