bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide Analysis of NPF, NRT2, CLC and SLAC1/SLAH Nitrate Transporters in Hexaploid Wheat (Triticum Aestivum)
Authors: Kumar Aman , Sandhu Nitika , Kumar Pankaj , Pruthi Gomsie , Singh Jasneet , Kaur Satinder , Chhuneja Parveen 
Published: September 2021

Abstract
Nitrogen transport is one of the most important processes in plants mediated by specialized transmembrane proteins. Plants have two main systems for nitrogen uptake from soil and its transport within the system - a low-affinity transport system and a high-affinity transport system. Nitrate transporters are of special interest in cereal crops because large amount of money is spent on N fertilizers every year to enhance the crop productivity. Till date four gene families of nitrate transporter proteins; NPF (nitrate transporter 1/peptide transporter family), NRT2 (nitrate transporter 2 family), the CLC (chloride channel family), and the SLAC/SLAH (slow anion channel-associated homologues) have been reported in plants. In our study, in silico mining of nitrate transporter genes along with their detailed structure, phylogenetic and expression analysis was carried out. A total of 412 nitrate transporter genes were identified in hexaploid wheat genome using HMMER based homology searches in IWGSC Refseq v2.0. Out of those twenty genes were root specific, 11 leaf/shoot specific and 17 genes were grain/spike specific. The identification of nitrate transporter genes in the close proximity to the previously identified 67 marker-traits associations associated with the nitrogen use efficiency related traits in nested synthetic hexaploid wheat introgression library indicated the robustness of the reported transporter genes. The detailed crosstalk between the genome and proteome and the validation of identified putative candidate genes through expression and gene editing studies may lay down the foundation to improve nitrogen use efficiency of cereal crops.
Anti-tumor effect of CTLA-4 antibody is independent of checkpoint blockade
Authors: Gao Han , Cai Haiyan , Zhang Fei , Liu Mingdong , Wang Xiaoxiao , Wang Pilin , Dou Fei , Li Fubin , Xu Ting , Zhou Aiwu 
Published: September 2021

Abstract
Antibodies targeting CTLA-4 are emerging as an important class of cancer therapeutics. It is assumed that these antibodies cause tumor rejection by blocking negative signaling from the CTLA-4-B7 interactions to enhance the priming of naïve T cells in lymphoid organs. However, recent findings have shown that the effectiveness of CTLA-4 antibody critically depends on the Fc domain and the host Fc receptors. It remains unclear if the blocking function of CTLA-4 antibody is required for its anti-tumor activity. To address this, here we have selected a non-blocking anti-CTLA-4 antibody (D138) and assessed its binding property and antitumor activity in comparison with the therapeutic CTLA-4 antibody ipilimumab. Crystal structures of CTLA-4 complexed with these antibodies show that D138 binds to a distinctly different site to that of ipilimumab on the CTLA-4 surface. D138 binding did not block the association of cells expressing CTLA-4 and B7 whereas ipilimumab did. Subsequent antitumor assay revealed that D138 was similarly effective as ipilimumab in inhibiting tumor growth in mice. This antitumor activity required Fc function for efficacy and was correlated with selective reduction of intratumor regulatory T (Treg) cells, resulting in a significant increase in the ratio of CD8+ over Treg cells. Overall these data clearly demonstrate that blocking CTLA-4-B7 interaction is not required for CTLA-4 antibody mediated antitumor activity, opening prospects of developing non-blocking CTLA-4 antibodies or simple binders towards other Treg surface markers for Treg-targeted immunotherapy.
The Safety, Feasibility, and Efficacy of Upper Limb Garment-integrated Blood Flow Restriction Training in Healthy Adults
Authors: Dhokia Bhavit , Mabin Elspeth Olivia , Bradley Warren Jeremy , Neal Bradley Stephen 
Published: September 2021

Abstract
Background Blood flow restriction training (BFR) has been demonstrated to increase muscle hypertrophy and strength, but has logistical and cost barriers. Garment-integrated BFR has the potential to reduce these barriers, by lowering equipment demands and cost at point of access. The primary aim of the study was to explore the safety and feasibility of garment-integrated BFR in the upper limb of healthy adults, with a secondary aim of exploring efficacy. MethodsParticipants who were active, otherwise healthy and had no previous experience with BFR, were sought. Eligible participants completed a five-week garment-integrated BFR programme that involved completing two sessions per week. Safety was determined by recording adverse events and by monitoring arterial occlusion pressure using a pulse oximeter. Feasibility was determined by measuring recruitment, adherence to the garment-integrated BFR programme and data collection. Efficacy was determined by measuring push-ups to volitional failure, arm girth, and number of prescribed repetitions completed. Adverse events were counted and reported as a percentage of the cohort. Adherence was calculated as a percentage of successfully completed sessions of the prescribed total. Mean change, 95% confidence intervals and associated effect sizes were calculated for efficacy outcomes. Results 28 participants were included and 27 successfully completed the study. Minimal adverse events were reported; one incident of localised bruising (0.36%) and three incidences of excessive pain during and post-exercise from two separate participants (1.07%). 3.7% of pulse oximeter readings were not recorded (82/2240). 278/280 sessions were successfully completed (adherence=99.3%). Mean push-ups to volitional failure increased by 40% (mean change=8.0, 95% CI 5.7, 10.3, d=1.40). Mean arm girth and mean number of prescribed repetitions completed were unchanged.Conclusions Garment integrated BFR is a safe and feasible option in the upper limb of healthy adults, with a secondary increase in push-ups to volitional failure also observed. Further studies are required to determine the efficacy of garment integrated BFR compared to other training methods, and the use of garment integrated BFR in other populations.
Risk factors for acute kidney injury after Stanford type A aortic dissection repair: a systemetic review and meta-analysis
Authors: Wang Lei , Zhong Guodong , Lv Xiaochai , Yi Dong , Hou Yanting , Dai Xiaofu , Chen LiangWan 
Published: September 2021

Abstract
Background Acute kidney injury (AKI) is one of the most common complications after Stanford type A aortic dissection (TAAD) repair surgery, but its risk factors are inconsistent in different studies. So this meta-analysis was conducted to systematically analyze the risk factors for AKI after TAAD repair surgery, so as to early identify the therapeutic targets for preventing AKI and to improve the outcomes. Methods Studies on risk factors for AKI after TAAD repair surgery were searched from PubMed, Embase, Cochrane library and Web of science from inception of databases to June 2021. The meta-analysis was performed by Stata 16.0 software. The combined incidence and risk factors of AKI and its impact on mortality after TAAD repair surgery were calculated. Results A total of 11 studies and 4156 patients were included. The combined incidence of postoperative AKI was 56.0%. The advanced age [odds ratio (OR)=1.32, 95% confidence interval (CI) (1.19, 1.47), P<0.001], cardiopulmonary bypass time > 180 minutes [OR=4.88, 95% CI (2.05, 11.59), P<0.001], red blood cell (RBC) volume transfused perioperatively [OR=1.13, 95% CI (1.03, 1.24), P<0.01], high body mass index [OR=1.22, 95% CI (1.18, 1.27), P<0.001] and preoperative renal malperfusion [OR= 5.32, 95% CI (2.92, 9.71), P<0.001] were risk factors for AKI after TAAD repair surgery. The in-hospital mortality [rate ratio (RR)=2.50, 95% CI (1.82, 3.44), P<0.001] and 30-day mortality [RR=2.81, 95% CI (1.95, 4.06), P<0.001] were higher in patients with postoperative AKI than that without AKI. Conclusions The incidence of AKI after TAAD repair surgery was high, and it increased the in-hospital and 30-day mortality. Reducing cardiopulmonary bypass time and RBC transfusions perioperatively, especially in elderly or patients with high body mass index, or patients with renal malperfusion preoperatively were important to prevent AKI after TAAD repair surgery.Systematic review registration number: INPLASY 202060100.
Development of a Prognostic Pyroptosis-Related Gene Signature for Head and Neck Squamous Cell Carcinoma Patient
Authors: Zhu Weiwen , Zhang Jiayi , Wang Mengyao , Zhai Rundong , Xu Yanbin , Wang Jie , Wang Mengqi , Zhang Hang , Liu Laikui 
Published: September 2021

Abstract
Objective: Head and neck squamous cell carcinoma (HNSCC) is a major threat to public health. Pyroptosis is a form of inflammatory programmed cell death that is still incompletely understood. The role of pyroptotic cell death in HNSCC remains to be fully defined. As such, the present study was developed to explore the potential prognostic utility of a pyroptosis-related gene (PRG) signature in HNSCC.Methods: PRG expression patterns and the associated mutational landscape in HNSCC were analyzed, after which a 6-gene prognostic model was constructed through least absolute shrinkage and selection operator (LASSO) and Cox regression analyses using the TCGA dataset, followed by validation with two GEO datasets (GSE41643 and GSE65858). Potential predictors of patient outcomes associated with this 6-gene model were identified through topological degree analyses of a protein-protein interaction network. Lastly, the prognostic value of NLRP3 as a predictor of HNSCC patient prognosis was established through immunohistochemical (IHC) analyses of samples from 176 HNSCC patients.Results: Differentially expressed PRGs were able to readily differentiate between HNSCC tumors and normal tissues. Risk scores derived from the 6-gene PRG model were independent predictors of HNSCC patient prognosis, and genes that were differentially expressed between low- and high-risk groups were associated with tumor immunity. IHC analyses further supported the value of NLRP3 as a predictor of HNSCC patient outcomes. Conclusions: Overall, these results highlight a novel prognostic gene signature that offers value in the context of HNSCC patient evaluation, although additional research will be essential to elucidate the mechanisms linking these PRGs to HNSCC outcomes.
Nordic Vaccination Strategies Face/off via Age Range Comparative Analysis on Key Indicators of COVID-19 Severity and Healthcare Stress Level
Authors: Islind Anna Sigríður , Óskarsdóttir María , Cot Corentin , Cacciapaglia Giacomo Cacciapaglia , Sannino Francesco 
Published: September 2021

Abstract
In this paper we analyze the impact of vaccinations on spread of the COVID-19 virus for different age groups. More specifically we examine the deployment of vaccines in the Nordic countries in a comparative analysis where we analyze factors such as healthcare stress level and severity of disease through new infections, hospitalizations, intensive care unit (ICU) occupancy and deaths. Moreover, we analyze the impact of the various vaccine types, vaccination rate on the spread of the virus in each age group for Denmark, Finland, Iceland, Norway and Sweden from the start of the vaccination period in December 2020 until the end of August 2021. We perform a three-fold analysis: i) frequency analysis of infections and vaccine rates by age groups, ii) rolling correlations between vaccination strategies, severity of COVID-19 and healthcare stress level and; iii) we also employ the epidemic Renormalization Group (eRG) framework. The latter is used to mathematically model wave structures, as well as the impact of vaccinations on wave dynamics. We further compare the Nordic countries with England. Our main results are the quantification of the impact of the vaccination campaigns on age groups epidemiological data, across countries with high vaccine uptake. The data clearly shows that vaccines markedly reduce the number of new cases and the risk of serious illness.
Utilization of personal protective equipment and associated factors among large-scale factory workers using health belief model in Debre-Berhan town, Amhara region, Ethiopia, 2021
Authors: Sema Wondimu , Tessema Muluken 
Published: September 2021

Abstract
BackgroundPersonal protective equipment is designed to protect workers from serious workplace injuries or illnesses resulting from contact with chemical, radiological, physical, electrical, mechanical, or other workplace hazards. ObjectiveTo determine Personal Protective Equipment utilization and its associated factor based on health belief model among large scale factory workers in Debre-Birhan, Ethiopia. MethodsAn institution-based cross-sectional study was employed in Debre Berhan Town, North Shoa Ethiopia from April 1 st to May 1 st , 2021 using an interviewer administered structured questionnaires. A total of 412 samples were selected by systematic random sampling method. The data was entered by Epi-data version 3.1 and analyzed by SPSS. variables with a p-value of 0.2 was fitted for multiple logistic regressions and a p-value of <0.05 was statistically significant. ResultA total of 412 workers were participated in the study with a 100% response rate. The mean age was 29 (±7.3) years. Most workers 367 (89 %) knew that PPE can prevent work related injury and illness. Over all 172 (41.7 %) of the workers were considered to have good PPE utilization. Perceived susceptibility [AOR=1.2, 95 %, CI (1.076-1.38)], perceived severity, [AOR=1.1, 95 %, CI (1.088-1.163)], perceived self-efficacy, [AOR=1.2, 95 %, CI (1.082-1.349)], and Perceived barrier [AOR=0.87, 95 %, CI (0.800 -0.956)] were found to be significant predictors of good PPE utilization. ConclusionThe study revealed that good Personal protective equipment utilization in large scale factory workers. Perceived susceptibility perceived severity, perceived barrier and perceived self-efficacy were found to be predictors of PPE utilization.
Exosomal microRNA-486-5p From Adipose Derived Stem Cells Alleviate Chondrocyte Apoptosis and Osteoarthritis by Attenuating Endoplasmic Reticulum Stress
Authors: Wang Yiming , Fan Aoyuan , Lu Liangyu , Pan Zhangyi , Ma Min , Luo Shulin , Liu Zheng , Yang Liqing , Cai Junfeng , Yin Feng 
Published: September 2021

Abstract
BackgroundAs one of the most common disabling diseases in the musculoskeletal system, osteoarthritis (OA) is characterized with cartilage matrix degeneration and chondrocyte apoptosis. Endoplasmic reticulum (ER) stress is well known for participate in chondrocyte apoptosis and cartilage degeneration in OA progression. microRNAs (miRNAs) could function in cartilage homeostasis, yet limited is known regarding whether miRNA could modulate ER stress in chondrocytes. Here, we reported that exosomal microRNA-486-5p from adipose derived stem cells (ADSCs) could alleviate chondrocyte apoptosis and osteoarthritis by attenuating ER stress MethodsER stress markers and inflammatory cytokines were analyzed in OA knee joint by immunohistochemistry and immunofluorescence staining. IL-1β induced apoptosis of chondrocytes was analyzed using flow cytometry. ER stress markers and inflammatory cytokines of IL-1β induced chondrocytes were analyzed by immunofluorescence staining, western blot and ELISA. miR-486-5p mimic overexpressed ADSCs and their exosomes were validated and used to treat IL-1β induced chondrocytes together with miR-486-5p mimic. Different administrative methods of miR-486-5p mimic were tracked both in vitro and in vivo, and further used to treat OA model mice. OA progression of mice was analyzed by H&E, safranin O/fast green, immunofluorescence and immunohistochemistry staining. ResultsWe validated the increased inflammation and ER stress in OA synovium and cartilage, and the IL-1β induced chondrocyte apoptosis was through the ER stress activation. Administration of exogenous miR-486-5p could not only inhibit the ER stress, but also alleviate chondrocytes apoptosis and promote matrix regeneration. In comparison with direct administration of miR-486-5p and miR-486-5p overexpressing ADSCs, exosomes seem to be a better delivery vehicle for miRNA in modulating chondrocyte homeostasis. Our immunofluorescence and IVIS imaging data further validated the better delivery ability of exosomes through tracking the uptake of miR486-5p in chondrocytes and the diffusion of miR-486-5p in the knee joint with different transportation methods. Exosomal microRNA-486-5p also showed a better effect on alleviating mice OA. ConclusionOur data demonstrated that exosomes are better delivery vehicle for miR-486-5p on alleviating chondrocyte apoptosis and osteoarthritis. This study provides evidence to this efficient strategy of exosomal miRNA delivery and to the miRNA-based therapy for OA.
STING Agonist Enhances the Efficacy of PD-L1 Monoclonal Antibody in Breast Cancer Immunotherapy by Activating the IFNβ Signaling Pathway
Authors: Yin Mingming , Hu Jinlong , Yuan Zhongxu , Luo Guangyi , Yao Jiaming , Wang Rundong , Liu Dongquan , Cao Baoqiang , Hu Zhiqi , Wu Wenyong 
Published: September 2021

Abstract
Purpose: This article focused on STING agonist role in breast cancer (BCa) immunotherapy.Methods: Clinical samples were collected from 37 BCa patients'. Xenograft tumor model was established by injecting 4T1 cells into mammary fat pad of mice. STING agonist and Atezolizumab were injected into mice with 2 times a week for 2 weeks. Peripheral blood, xenograft tumor, lung, liver, brain-cortex and kidney of mice were collected. Anti-IFNAR1 was used to treat 4T1 cells. Quantitative reverse transcription-polymerase chain reaction and Western blot were used for mRNA and proteins expression. Enzyme-linked immunosorbent assay, immunohistochemistry and hematoxylin-eosin staining were performed. Results: Tumor tissues of BCa patients exhibited lower STING and high PD-1 and PD-L1 protein expression. STING agonist inhibited 4T1 cells growth in mice (P < 0.001). STING agonist increased IFNβ level and the phosphorylation of STING, TBK1, IRF3 and STAT1 in xenograft tumor (P < 0.001). STING agonist synergized with Atezolizumab to inhibit 4T1 cells growth in mice, and increase TNF-α, IFN-β and IL-10 level in peripheral blood and xenograft tumor (P < 0.01). STING agonist synergized with Atezolizumab to increase CD8+ cytotoxic T cells and decrease FOXP3+ Tregs cells in xenograft tumor. STING agonist was non-toxic to lung, liver, brain-cortex and kidney. Anti-IFNAR1 reversed STING agonist promotion on TBK1, IRF3 and STAT1 phosphorylation in 4T1 cells (P < 0.01).Conclusion: STING agonist enhances the efficacy of Atezolizumab in BCa immunotherapy by activating the IFNβ signaling pathway.
Seasonal Patterns and Trends of Air Pollution in The Upper Northern Thailand from 2004 to 2018
Authors: Sukkhum Sarawut , Lim Apiradee , Saelim Rattikan , Ingviya Thammasin 
Published: September 2021

Abstract
The objective of this study was to investigate the seasonal patterns and trends of air pollutants in upper northern Thailand (UNT) from 2004 to 2018. The hourly air pollutant concentration data recorded from 6 monitoring stations in the UNT were obtained from the Pollution Control Department, Ministry of Natural Resources and Environment of Thailand. Cubic splines were used to assess seasonal patterns and trends of air pollutants. Linear regression was used to estimate the average increase in concentrations of air pollutants at each monitoring station. The results exhibited seasonal patterns for CO, NOX, NO2, O3, and PM10, in all stations while SO2 only in one station in Lampang and all stations in Chiangmai. The concentrations of these pollutants rose during August and September and reached peak levels between March and April. In the past 15 years, the levels of overall CO, O3, and SO2 in the UNT had significantly increased, on average of 0.032 ppm, 0.012 ppb, and 0.017 ppb, respectively. In contrast, NO2, NOX, and PM10 had significantly decreased on average of 0.012 ppb, 0.011 ppb, and 0.016 mg/m3, respectively. In conclusion, it should be of concern for such activities that related to air pollutants variation accordingly.
Changes in DNA methylation during pregnancy and after delivery
Authors: Lin Ming-Wei , Tsai Mong-Hsun , Shih Ching-Yu , Tai Yi-Yun , Lee Chien-Nan , Lin Shin-Yu , Li Hung-Yuan 
Published: September 2021

Abstract
Background

Gestational adaptation takes place soon after fertilization and continues throughout pregnancy, while women return to a pre-pregnancy state after delivery and lactation. However, little is known about the role of DNA methylation in the fine tuning of maternal physiology. In this study, we investigated whether and how the DNA methylation pattern changes in the three trimesters and after delivery in ten uncomplicated pregnancies.
Results

DNA methylation was measured using Human MethylationEPIC BeadChip. There are 14,018 CpG sites with statistically significant changes in DNA methylation over the four time periods (p < .001). Overall, DNA methylation of the non-pregnant state was higher than that of the three trimesters (p < .001), with the protein ubiquitination pathway the top canonical pathway involved. We classified these CpG sites into nine groups according to the changes in the three trimesters. During pregnancy, most CpG sites (61.63%) had subtle or no changes in DNA methylation (Group 9). There were 3,173 (22.64%) CpG sites in Group 7 and 995 (7.1%) CpG sites in Group 8, which were the two groups with DNA methylation changes between the first and second trimesters. The top systems involved in these two groups were associated with embryonic development and organ morphological changes, as shown by the IPA analysis.
Conclusion

The DNA methylation pattern changes between trimesters, which may be involved in maternal adaptation to pregnancy. Meanwhile, the DNA methylation patterns during pregnancy and in the postpartum period were different, implying that puerperium repair may also act through DNA methylation mechanisms.
Melanoma Detection By AFM Indentation of Histological Specimens
Authors: Jeon ByoungJun , Jung Hyo Gi , Lee Sang Won , Lee Gyudo , Shim Jung Hee , Kim Mi Ok , Kim Byung Jun , Kim Sang-Hyon , Lee Hyungbeen , Yoon Dae Sung , Jo Seong Jin , Choi Tae Hyun , Lee Wonseok 
Published: September 2021

Abstract
Melanoma is visible unlike other types of cancer, but it is still challenging to diagnose correctly because of the difficulty in distinguishing between benign nevus and melanoma. We conducted a robust investigation of melanoma, identifying considerable differences in local elastic properties between nevus and melanoma tissues by using atomic force microscopy (AFM) indentation of histological specimens. Specifically, the histograms of the elasticity of melanoma displayed multimodal Gaussian distributions, exhibiting the heterogeneous mechanical properties, in contrast with the unimodal distributions of elasticity in the benign nevus. We identified this notable signature was consistent regardless of blotch incidence by sex, age, anatomical site (e.g., thigh, calf, arm, eyelid, and cheek), or cancer stage (I, IV, and V). In addition, we found that the non-linearity of the force-distance curves for melanoma is increased compared to benign nevus. We believe that AFM indentation of histological specimens may technically complement conventional histopathological analysis for earlier and more precise melanoma detection.