bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of sentinel plant species for evaluating phytotoxicity of veterinary antibiotics in mediterranean europe
Authors: García Rosa M. , Martínez-Fernández Jesús , Rodríguez Antonio , Torre Ana de la 
Published: November 2021

Abstract
Background
Antibiotics used to treat livestock species enter agricultural fields when they are excreted by grazing animals or are present in manure that is added to fields as fertiliser. In the European Union, the potential effects of such antibiotics on terrestrial plants must be evaluated following the standardised OECD 208 method, which specifies the crop and wild species that should serve as “sentinels” for assessing antibiotic exposure. The present study aimed to compare this approved list of sentinel species against crop and wild plant species actually present in agricultural and pasture lands in Mediterranean Europe in order to identify the most appropriate sentinel plants for the region. The study focused on Spain as a region representative of Mediterranean Europe. Georeferenced layers for wild plant species and cultivated areas (crops), livestock density and land cover were combined, and then selection criteria were applied, leading to the identification of sentinel crop species for agriculture and pasture scenarios.
Results
In the agriculture scenario, the sentinel crop species were barley, wheat, corn, sunflower, dried pie, alfalfa, vetch, oilseed rape and sugar beet; the sentinel wild species were Papaver rhoeas, Galium aparine and Chenopodium album. In the pasture scenario, sentinel wild species were Bromus tectorum, Agrostis capillaris, Trifolium pratense, Lotus corniculatus and Galium aparine. The following common weed species in field boundaries or in pasture lands also emerged as potential sentinel species for risk assessment, even though they are not listed in the OECD 208 method: Sonchus oleraceus, Avena sterilis, Dactylis glomerata, Hordeun murinum and Lolium rigidum.
Conclusions
The sentinel species identified in this study may be useful in risk assessment procedures covering Mediterranean Europe. The method developed for this study could be useful for identifying sentinel species for other geographical areas.
Comparison of Pedicle Screw Fixation With or Without Cement Augmentation Combined With Single-segment Isthmic Spondylolisthesis in Osteoporotic Spine
Authors: Peng Jian-cheng , Guo Hui-zhi , Zhan Chen-guang , Huang Hua-sheng , Ma Yan-huai , Zhang Shun-cong , Xu Yue-rong , Mo Guo-ye , Tang Yong-chao 
Published: November 2021

Abstract
PurposeThis study aims to investigate the necessity of cement-augmented pedicle screw fixation in single-segment isthmic spondylolisthesis with osteoporosis.MethodFifty-nine cases were reviewed retrospectively. Thirty-three cases were in the polymethylmethacrylate-augmented pedicle screw (PMMA-PS) group, and the other 26 cases were in the conventional pedicle screw (CPS) group. Evaluation data included operation time, intraoperative blood loss,hospitalization cost, hospitalization days, rates of fusion, screw loosening, bone cement leakage, visual analog scores (VAS) , Oswestry disability index (ODI) , Lumbar Lordosis（LL）, Pelvic Tilt（PT） and Sacral Slope（SS）. ResultsThe operation time and blood loss in the CPS group decreased significantly compared to the PMMA-PS group (P < 0.05). The average hospitalization cost of the PMMA group was significantly higher than that of the CPS group (P < 0.05). There was no significant difference for the average hospital stay between the 2 groups (P > 0.05). The initial and the last follow-up postoperative VAS and ODI improved significantly in the two groups (P < 0.05). There were no significant differences in VAS and ODI at each time point between the 2 groups (P > 0.05). The last postoperative spine-pelvic parameters were significantly improved compared with preoperation (P < 0.05). In the PMMA-PS group, the fusion rate was 100%. The fusion rate was 96.15% in the CPS group. No significant difference was found between the two groups for the fusion rate (P > 0.05). Nine cases in the PMMA-PS group had bone cement leakage (27.27%). There was not screw loosening in the PMMA-PS group. There were 2 cases of screw loosening in the CPS group. There were no significant differences in screw loosening, postoperative adjacent segment fractures, postoperative infection or postoperative revision between the 2 groups (P > 0.05). ConclusionsThe use of PMMA-PS on a regular basis is not recommended for posterior lumbar interbody fusion for the treatment of single-segment isthmic spondylolisthesis with osteoporosis.
Knowledge and Attitude Toward Emergency Contraceptive Pills Among First-Year Undergraduate Students in Southern Thailand
Authors: Yongpraderm Siranee , Uitrakul Suriyon 
Published: November 2021

Abstract
Background: The objective of this study was to investigation of the knowledge and attitude towards emergency contraceptive pills (ECPs) among first-year undergraduate students in a university in Thailand.Methods: This cross-sectional survey study was performed using the developed questionnaires that was validated by four experts. The questionnaires were distributed to all the first-year students in the university via an online platform. The characteristic data were descriptively analyzed and the knowledge data were analyzed using Chi-square test, Mann-Whitney U test and one-way ANOVA.Results: A total of 335 students who responded to the questionnaires and met the eligible criteria for the study was analyzed. The mean knowledge score of all respondents was 7.76±0.15 out of 15. The most correct-answered questions were the questions relating to efficacy and safety of ECPs in pregnant women (78.5% and 72.2% corrected, respectively). On the contrary, the least correct-answered questions were about the ECP regimens and using ECPs instead of combined oral contraception (COC) (30.4% and 34.9%, respectively). In addition, the results indicated that experience in using ECPs and in ECP education were significant factors in high scores of knowledge. Moreover, most respondents trusted and would like to receive the information on ECPs from health professionals in hospitals, academic institutions, or pharmacies.Discussion: The average knowledge of ECPs of first-year students in a university in Thailand was at a moderate level. More knowledge about the regimens of the drug and using ECPs instead of COC should be advised to students, particularly at the university or pharmacies, and should be done by healthcare staff.
N6-adenosine methylation of mRNAs requires Wtap expression and controls T cell receptor signaling and survival
Authors: Ito-Kureha Taku , Leoni Cristina , Borland Kayla , Bataclan Marian , Metzger Rebecca , Ammann Gregor , Krug Anne , Marsico Annalisa , Kellner Stefanie , Canzar Stefan , Feske Stefan , Monticelli Silvia , König Julian , Heissmeyer Vigo 
Published: November 2021

Abstract
T cell antigen receptor (TCR) signaling controls the development, activation and survival of T cells by involving several layers and numerous mechanisms of gene regulation. N6-methyladenosine (m6A) is the most prevalent mRNA modification affecting splicing, translation and stability of transcripts. Here, we describe the Wtap protein as essential for m6A methyltransferase complex function and reveal its crucial role in TCR signaling. Wtap and m6A methyltransferase functions were required for the differentiation of thymocytes, control of activation-induced death of peripheral T cells and prevention of colitis by enabling gut RORγt+ regulatory T cell function. Transcriptome and epitranscriptomic analyses reveal that m6A modification destabilizes Orai1 and Ripk1 mRNAs. Lack of post-transcriptional repression of the encoded proteins correlated with increased store-operated calcium entry (SOCE) activity and diminished survival of T cells. These findings uncover how m6A modification impacts on TCR signal transduction and determines activation and survival of T cells.
Turing miRNA Into Infinite Coordination Supermolecule: A General and Enabling Nanoengineering Strategy for Resurrecting Nuclear Acid Therapeutics
Authors: Li Liya , He Wangxiao , You Weiming , Yan Jin , Liu Wenjia 
Published: November 2021

Abstract
Background
Clinical translation of therapeutic nuclear acid, particularly those targeting tumor progression, has been hampered by the intrinsic weaknesses of nuclear acid therapeutic including poor systemic stability, rapid clearance, low membrane permeability and lack of targeting ability. Small nuclear acid engineered into carrier-free nanodrugs with structural stability and disease targeting may be viable to overcome pharmaceutical obstacles of nuclear acid.
Methods
A general method through a mild and simple chemistry was established to convert therapeutic miRNA into an infinite Auric-sulfhydryl coordination supramolecular miRNA termed IacsRNA with near-spherical nanostructure, high colloid as well as anti-hydrolysis stability and low macrophage uptakes.
Results
IacsRNA presented the increased half-life period in circulation and accumulation at tumor sites in comparison to normal miRNA. Moreover, Iacs-miR-30c showed no toxicity of viscera and sanguis system in the 5-time injection dosage of the treatment. More importantly, Iacs-miR-30c potently suppressed the Wnt signaling pathway in vitro and in vivo, and effectively sensitized both potency of 5-Fu in PDX model of colon cancer and Anti-PD1 in B16F10 homograft model of melanoma.
Conclusion
Collectively, this work amply confirmed the design of IacsRNA as a general and viable strategy of nano-pharmaceutic to concert flimsy therapeutic miRNA into potential drugs. Considering from a broader perspective, the miRNA-initiated infinite coordination self-assembly strategy has distinct advantages in resurrecting nuclear acid therapeutics, probably bringing new inspiration to RNA-derived therapeutics of a great variety of human diseases including cancer.
Quantitative Proteomic Analysis of Preventive Potential of Aspirin for Colon Cancer Cells
Authors: Han Wei , Zhang Yan , Sun Haitao , Ji Yu , Wang Rong 
Published: November 2021

Abstract
Objective: To further systematically understand the molecular mechanisms that aspirin prevents colon carcinogenesis.Methods: We detected the global protein expression profiles of colorectal cancer along with the treatment of aspirin by a quantitative proteomic approach. We analyzed the proteomic results using bioinformatics（including differential proteins, protein annotation, Kegg Pathways and protein-protein interaction network ）. Cell viability of HT29 cells treated with aspirin was determined by CCK8 assay. The expression of differential proteins p53 and CDK1 were quantified by real-time PCR and Western blot. We measured cell cycle distribution and cell apoptosis of H1299 cells exposed to aspirin by flow cytometric analysis. Results: We found 552 proteins that were significantly dysregulated after10mM aspirin treatment of colon cancer cells. Further enrichment analysis of the dysregulated proteins suggested that cell cycle-related proteins are the most differential proteins such as p53, CDK1, CyclinB, Chk1, Chk2 and CyclinD. The results of real-time PCR and Western blot showed that p53 and CDK1 obvious upregulation after aspirin exposed to colon cancer cells. We also detected that aspirin promoted the G1/S arrest of cell cycle in HT29 cells. We confirmed aspirin induced cell apoptosis in human HT29 colon cancer cells with concentration-dependent increase. Conclusions: The result indicated that aspirin induced colorectal cancer cells G1 arrest and cell apoptosis by p53-CDK1 pathway. Accordingly, aspirin may represent a promising preventive candidate for colon cancer.
SARS-COV2 Seroprevalence in a Cohort of Perinatally HIV Infected Children and Young Adults From May to December 2020 in Italy
Authors: Tumeo Chiara Casamento , Cotugno Nicola , Coltella Luana , Ranno Stefania , Piccioni Livia , Linardos Giulia , Colagrossi Luna , Concato Carlo , Perno Carlo Federico , Bernardi Stefania 
Published: November 2021

Abstract
SARS-CoV2 is a new coronavirus which started spreading in December 2019 from Wuhan, China. The seroprevalence of SARS-CoV2 antibodies allows to define a better picture of the spread of SARS-CoV2 infection in the population. The duration of SARS-CoV2 antibodies in the healthy population as well as in immunocompromised patients is still a topic of debate. HIV-infected people are at increased risk of developing complications from contracting a viral illness. Furthermore,their ability to develop and maintain an optimal immunological response to any kind of pathogen appears to be reduced.We analyzed the overall seroprevalence of SARS-CoV2 antibodies in 85 HIV infected-people on ART aged between 5 and 34 years old from May to January 2021. 88,2%of patients were in a good state of viroimmunological control: 23 showed a VL<40cp/ml and 52 had an undetectable VL. When positive for SARS-CoV2 serology, a confirmatory nasopharyngeal swab for PCR assessment and a second serological assay would be performed.Out of the 85 patients, 5 proved to be positive for SARS-CoV2 antibodies (rate of prevalence 5.8%). In all 5 cases the nasopharyngeal swabs were negative and the second assay for SARS-CoV2 antibodies performed in 4 out of 5 patients a week later was negative as well. The anamnestic recall brought no elements of suspicion for a past infection.The duration of SARS-CoV2 antibodies after COVID19 disease is still poorly understood in healthy population and additional studies will be needed to define the durability of humoral responses in immunocompromised children and in particular in HIV infected children under effective ART. It is still unknown whether ART or their immunological impairment may in part mitigate the pathogenesis of SARS-CoV-2 infection. Also, it will be interesting to analyze the impact of vaccination against SARS-CoV2 in HIV infected patients with a satisfactory virological control.
Engineering of AAV-Mediated in Vivo Targeted DNA Methylation Editing System via Staphylococcus Aureus Derived Cas9-SunTag
Authors: Yamamoto Naoki , Morita Sumiyo , Hatada Izuho , Ideta-Otsuka Maky , Tamura Hideki , Narita Minoru , Igarashi Katsuhide 
Published: November 2021

Abstract
DNA methylation aberrations have been implicated in the pathogenesis of various psychiatric and developmental disease states. However, basic research and therapeutic in vivo applications targeting aberrant DNA methylation are still limited due to the lack of targeted DNA methylation editing systems that work on capacity-limited adeno-associated virus (AAV), a highly versatile in vivo gene delivery vector. Here, we report the engineering of AAV-based vector system for in vivo targeted DNA methylation/demethylation by integrating small Cas9 orthologues (SaCas9) and a dCas9-SunTag methodology. In this system, dSaCas9-SunTag targeting protein and anti-SunTag-mini-antibody (scFv) fused effector protein were packaged into different vectors for efficient in vivo delivery by AAV. We demonstrated that co-introduction of AAV vectors carrying dSaCas9-SunTag and scFv-fused Dnmt3A, Dnmt3L, or Dnmt3A-Dnmt3L fusion proteins induced robust DNA methylation on the Bdnf gene locus in a guide RNA dependent manner in vitro. The scFv-fused TET1 and TET2 successfully induced robust targeted DNA demethylation in the H19 ICR. We also constructed a doxycycline (Dox)-inducible target DNA methylation system utilizing dSaCas9-SunTag and scFv-Dnmt3AL. Finally, we showed that AAV-mediated delivery of dSaCas9-SunTag system induced DNA methylation on the Bdnf gene locus and suppressed activity-dependent but not basal Bdnf expression after contextual fear learning in the Hippocampus of adult mouse. Our in vivo targeted DNA methylation editing system can be a promising platform for understating the causal relationship between psychiatric disease and aberrant DNA modifications.
Synthesis and Evaluation of Technetium-99m-labeled pH (low) Insertion Peptide Variant 7 for Early Diagnosis of MDA-MB-231 Triple-Negative Breast Cancer by Targeting the Tumor Microenvironment
Authors: Chen YueHua , Su Yuan , Pang XuFeng , Song XiaoXia , Zhao WanJun , Yu MingMing 
Published: November 2021

Abstract
Objective To prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 (pHLIP(Var7)) and carry out imaging of tumor-bearing nude mice in vivo, to study its value in the early diagnosis of triple-negative breast cancer (TNBC).Methods The pHLIP(Var7) sequence was synthesized by solid-phase polypeptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP(Var7) to form a strong chelating group containing an N4 structure. The polypeptide was directly labeled with 99mTc to determine the in vitro binding propensity of 99mTc-pHLIP(Var7) to MDA-MB-231 cells, to measure the in vivo biodistribution of 99mTc-pHLIP(Var7) in tumor-bearing nude mice, and to perform small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) of these mice.Results The radiochemical yield and radiochemical purity of 99mTc-pHLIP(Var7) were 99.49%±0.17% and 99.63±0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP(Var7) and MDA-MB-231 cells continuously increased in an acidic environment, being significantly higher than their cell binding fraction (P < 0.01) when pH = 7.4 and the cell binding fraction (P < 0.01) of 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P < 0.01). The biodistribution assay showed that the distribution of 99mTc-pHLIP(Var7) in tumors at each time point was significantly higher than that of 99mTc-kVar7 (P < 0.01). 99mTc-pHLIP(Var7) and 99mTc-kVar7 were also significantly distributed in the liver. SPECT/CT imaging was basically consistent with the biodistribution results. The tumor was clearly imaged at each time point after injection of 99mTc-pHLIP(Var7) but could not be imaged after injection of 99mTc-kVar7. The liver was clearly imaged at each time point in both groups.Conclusion 99mTc-pHLIP(Var7) has high radiochemical yield and stability, and it concentrates highly in tumor tissues. The presence of a very strong radioactive background in the abdomen of tumor-bearing nude mice does not preclude the early diagnosis of TNBC.
Precipitation Pattern Alters the Effects of Nitrogen Deposition on the Growth of Alien Species Robinia Pseudoacacia
Authors: Wang Xiao , Guo Xiao , Ding Wenli , Du Ning , Guo Weihua , Pang Jiayin 
Published: November 2021

Abstract
Aims
Nitrogen (N) supply and precipitation pattern (amount and frequency) both affect plant growth. However, N deposition is increasing and precipitation regimes are changing in the context of global change. An experiment was conducted to determine the effect of precipitation pattern and N supplies on the growth of a widely distributed and planted N2-fixing alien species Robinia pseudoacacia.
Methods
Seedlings were grown in a glasshouse at four different N levels combined with different precipitation regimes, including three precipitation amounts, and two precipitation frequencies. After treatment for 75 days, plant height, biomass allocation, leaf and soil nutrient concentrations were measured.
Results
Plants under high precipitation frequency had greater biomass compared with plants lower precipitation frequency with the same amount of precipitation. Higher N supply decreased biomass allocation to nodules. Nodule growth and N2 fixation of R. pseudoacacia with low precipitation amount was more inhibited by high N deposition compared with plants received higher precipitation amount. Slightly N deposition under higher precipitation inhibited N2 fixation but did not fulfil the N need in plants.
Conclusions
Nitrogen deposition might inhibit N2 fixation of plants even in low level but low nitrogen in soil cannot fulfil the N need of plants, and caused N2 fixation limitation in plants during seedling stage. There was likely a shift from acquiring N mainly from N2 fixation to acquisition of N directly with root when N supply was increased. High N deposition level, and increased precipitation frequency might increase the invasion risk of R. pseudoacacia.
Aquatic Toxicity Integrated Testing and Assessment Strategies (ITS) for Difficult Substances: Case Study With Thiochemicals
Authors: Nendza Monika , Ahlers Jan 
Published: November 2021

Abstract
Background An Integrated Testing and Assessment Strategy (ITS) for aquatic toxicity of 16 thiochemicals to be registered under REACH revealed 12 data gaps, which had to be filled by experimental data. These test results are now available and offer the unique opportunity to subject previous estimates obtained by read-across (analogue and category approaches) to an external validation. The case study thiochemicals are so-called difficult substances due to instability and poor water solubility, challenging established ITS. Results The new experimental data confirm the previous predictions of acute aquatic toxicity with the new test results indicating a 2-5 times lower toxicity than previously predicted. The previous predictions thus are conservative and closer to the experimental results than expected. The good agreement can be attributed to the fact that we had limited the extrapolations to narrow chemical groups with similar SH-group reactivities. The new experimental data further strengthen and externally validate the existing trends based on similarity in chemical structures, mode of action (MoA), water solubility and stability of source and target compounds in aquatic media. Based on the new experimental data, reliable revised PNECs could be derived and the REACH requirements for these thiochemicals are largely fulfilled. Appropriately adapted ITS are therefore able to reduce in vivo tests with fish even for difficult substances and replace them with alternative information. Conclusions Both experimental and alternative information for difficult substances such as thiochemicals that are rapidly transformed in water are subject to considerable uncertainty. For example, the use of nominal, initial or time-weighted average concentrations, contribute variability in the determination of aquatic toxicity. The use of nominal concentrations is likely to be the most appropriate choice as it reflects realistic worst-case environmental conditions in these cases. In general, uncertainties in (historical) test results and alternative information (read-across) must be considered in terms of how much uncertainty is acceptable for environmental protection on the one hand and how much certainty is technically feasible on the other.