bluuebunny/crossref_metadata_2025_split huggingface dataset:
NR4A1 suppresses cancer replication stress through R-loop-dependent inhibition of immediate early gene transcriptional elongation
Authors: Haber Daniel , Guo Hongshan , Golczer Gabriel , Wittner Ben , Langenbucher Adam , Zachariah Marcus , Dubash Taronish , Hong Xin , Comaills Valentine , Burr Risa , Horwitz Elad , Vuille Joanna , Wiley Devon , Reeves Brittany , zhang Jiamin , Niederhoffer Kira , Lu Chenyue , Wesley Benjamin , Ho Uyen , Toner Mehmet , Zou Lee , Mostoslavsky Raul , Maheswaran Shyamala , Lawrence Michael 
Published: November 2020

Abstract
Deregulation of oncogenic proliferative signals triggers replication stress in cancer cells to which they must adapt1,2. Immediate early genes (IEGs), identified by their rapid stress-induced transient bursts of expression, are critical to integrating downstream signaling pathways3,4. In studying tumor initiation by patient-derived breast cancer cells, we observed acquisition of open chromatin domains at the genebody and 3’-UTR of IEGs, uniquely across the genome. Through in vivo and in vitro modeling, we show that the IEG and orphan nuclear receptor NR4A15 localizes across multiple IEG genebodies, where it binds to RNA Pol II, arresting transcriptional elongation and generating extensive R-loops and accessible chromatin. Acute stress promptly removes NR4A1 from IEG genebodies, triggering immediate release of their poised transcripts. In breast cancer cells, NR4A1 overexpression increases tumorigenesis; conversely, its deletion leads to uncompensated replication stress, chromosomal instability and mitotic catastrophe, driven by deregulation of its IEG target FOS. A large fraction of primary breast and other cancers exhibit open genebody chromatin at IEGs, consistent with preserved NR4A1 function. Thus, NR4A1 mediates a novel transcriptional elongation checkpoint, unique to stress-induced genes and required for their rapid bursts of expression. Cancers that have retained this mechanism in adapting to chronic replication stress may be dependent on NR4A1 for proliferation.
In situ structure determination using single particle cryo-electron microscopy images
Authors: Cheng Jing , Li Bufan , Si Long , Zhang Xinzheng 
Published: November 2020

Abstract
Cryo-electron microscopy (cryo-EM) tomography is a powerful tool for in situ structure determination. However, this method requires the acquisition of tilt series, and its time consuming throughput of acquiring tilt series severely slows determination of in situ structures. By treating the electron densities of non-target protein as non-Gaussian distributed noise, we developed a new target function that greatly improves the efficiency of the recognition of the target protein in a single cryo-EM image without acquiring tilt series. Moreover, we developed a sorting function that effectively eliminates the false positive detection, which not only improves the resolution during the subsequent structure refinement procedure but also allows using homolog proteins as models to recognize the target protein. Together, we developed an in situ single particle analysis (isSPA) method. Our isSPA method was successfully applied to solve structures of glycoproteins on the surface of a non-icosahedral virus and Rubisco inside the carboxysome. The cryo-EM data from both samples were collected within 24 hours, thus allowing fast and simple structural determination in situ.
Analysis of drug resistance in Helicobacter pylori by complete genome sequencing in Bama County, Guangxi, China
Authors: huang yanqiang , Li Xiao-Hua , Huang Yong-Yi , Luo Xian-ke , Zhao Li-juan , Li Ru-Jia , Qin Yan-Chun , Dai Yuan-Yuan , Qin Chun , Chen Hao 
Published: November 2020

Abstract
The resistance rate of clinical Helicobacter pylori (Hp) isolates has increased, however, the mechanism of drug resistance is unclear. In this study, we isolated drug-resistant Hp strains isolated from different areas and different populations of China for genomic analysis. The aim of this study was to investigate drug resistance in Hp from Bama County, Guangxi, China. Minimal inhibitory concentrations (MICs) of clarithromycin, metronidazole and levofloxacin were determined and complete genome sequencing was performed with annotation. The presence of hp1181 and hp1184 genes was detected by RT-PCR. The relationships between hp1181, hp1184 and clarithromycin resistance were confirmed by gene mutation and drug-resistant strains. Three drug-resistant Hp strains were isolated from patients with gastritis in Bama County. The strains showed a high degree of homology with hp26695 through complete genome detection and identification. Differences in genome sequences, gene quantity and gene characteristics were detected amongst the three strains. Prediction and analysis of the function on drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains that were the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains increased significantly. In summary, The expressions of the genes hp1184 and hp1181 were associated with clarithromycin resistance in the Hp from Bama, Guangxi.
Clinical effect of 3.0% hydrogen peroxide containing bleaching patch with primer in a double-blind randomized controlled trial
Authors: Kim Jin-Kyoung , Youn Ha-Young , Jin Myoung-Uk , Ahn Jae-Hyun , Bang Seung-Eun , Choi Youn-Hee , Song Keunbae 
Published: November 2020

Abstract
Background: To clinically evaluate the efficacy and safety of a primer that contains taurine and self-bleaching patches containing 3.0% hydrogen peroxide.Methods: Overall, 55 participants were selected in this double-blinded randomized clinical trial between March and May 2019. Bleaching patches containing 3.0% hydrogen peroxide were attached using the primer on the labial surface of the upper six anterior teeth for 30 min once daily. △E* values of color changes were measured using Shade Eye NCC for determining the efficacy of bleaching on days 3, 5, 7, and 10 before and after attachment. The safety was assessed using gingival index and visual analog scale for tooth sensitivity and gingival irritation, respectively.Results: △E* values were visibly detected from day 7 after the attachment of patches, and the bleaching effect was identifiable. No statistically significant difference was observed in the gingival index (p = 0.069), tooth sensitivity (p = 0.983), and gingival irritation (p = 0.518).Conclusions: When the self-bleaching patches using 3.0% hydrogen peroxide with the primers were attached for 30 min once daily, visible bleaching effect was observed from day 7 of attachment, and it was verified to be safe for use without any significant adverse effect.Clinical Relevance: This study was conducted after securing safety for clinical trials.Trial registration: ISRCTN63650330
Establishment of narrow root fracture models using modified temperature cycling method and diagnosis using different cone-beam CT units
Authors: Liang Jiahao , Wang Tiemei , Cao Dantong , Cao Ya , Gao Antian , Xie Xin , Wang Zhiyong , Lin Zitong 
Published: November 2020

Abstract
AimUsing modified thermal cycling method to establish narrow root fracture models and evaluate the diagnosis efficiency of them using four different cone-beam CT (CBCT) units.MethodologyFifty-six intact teeth were selected and the crowns of the teeth were embedded using general purpose acrylic resin. 50 VRF models were established by soaking these teeth in liquid nitrogen and hot water cyclically; 6 teeth were used as negative control. All the 56 teeth were scanned with the smallest voxel size of four different CBCT units (NewTom VGi, Planmeca Promax 3D Max, Kavo 3D eXam and Soredex Scanora3D). The CBCT images were evaluated for the presence or absence of fracture lines. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC) were calculated for the diagnosis of FLs using the four CBCT units. After that, 10 VRF teeth were randomly selected and the roots were sliced using slow-speed saw to obtain horizontal root sections with thickness of 2mm from enamel-cemental junction to the root apex and 25 root sections were finally obtained. Scanning electron microscope (SEM) was used to measure the width of the fracture lines (FLs) for each root section at one side.ResultsFifty narrow root fracture models were successfully established. There were totally 50 positive VRF models with 83 FLs and 6 negative VRF models. The diagnosis sensitivity was 0.24, 0.38, 0.29 and 0.19, the diagnosis specificity was 0.45, 0.16, 0.55, and 0.75, and the AUC was 0.60, 0.52, 0.59 and 0.61 for NewTom VGi, Planmeca Promax 3D Max, Soredex Scanora-3D and Kavo 3D eXam respectively. Randomly selected 10 models were sliced and 25 root sections with 45 FLs were acquired. The width of FLs was from 3.43μm to 143μm; 32.06% were less than 25μm, only 9.6% were from 75 to 150μm with SEM.ConclusionsThe modified temperature cycling method is a simple and effective method to establish narrow root fracture models, the diagnosis efficiency for these narrow fracture lines were quite poor using all the four different CBCT units.
Prevalence Of Bacterial Urinary Tract Infection And Antimicrobial Susceptibility Patterns Among Diabetes Mellitus Patients Attending Zewditu Memorial Hospital, Addis Ababa, Ethiopia
Authors: Worku Gebremedhin Yenehun , belete Yerega alamneh , Abegaz Woldaregay Erku 
Published: November 2020

Abstract
Background: Urinary tract infection (UTI) is caused by colonization and growth of microorganisms within the urinary system. Diabetic patients are more prone to bacterial urinary tract infections due to impaired host defense and high glucose concentration in urine. Surveillance of urinary tract pathogens and their antibiogram is a key to patient management. The aim of this study was to determine the prevalence of bacterial UTI and antimicrobial susceptibility patterns (AST) among diabetes patients. Methods: Hospital-based cross-sectional study was conducted from May to July, 2018. Two hundred twenty-five mid-stream urine samples were collected for culture and identification based on the standard protocol. Antimicrobial susceptibility test was done for all positive urine cultures by Kirby Bauer's disk diffusion method based on CLSI guidelines. Data were entered into Epi-data version 3.2.1 and exported to the Statistical Package for the Social Science (SPSS) version 20 statistical software. Binary and multiple logistic regression test results were used.Results: The study result revealed 9.8% overall UTI prevalence. Five species of bacterial uropathogens were isolated. Among these, E. coli (63.6%) was the leading followed by K. pneumoniae (13.6%). In this study, significant bacteriuria was strongly associated with duration of diabetics, previous UTI and symptomatic UTI. Gram-negative bacterial isolates showed high level of sensitivity (100%) to nitrofurantoin and meropenem. On the contrary, high level of resistance (100 %) for ampicillin, doxycycline, cefuroxime, and (94.4 %) amoxacillin-clavulanate were observed. No resistance was observed among gram positive bacterial isolates except penicillin (100 % resistance). Over all prevalence of MDR was 100 % For Gram-negative bacteria.Conclusion: Presence of previous urinary tract infection and duration of diabetes were found as important factors that increase the prevalence of UTI among diabetes patients. This study also showed high prevalence of drug resistance to doxycycline, amoxacillin-clavulanate, cefuroxime and penicillin for both Gram- negative and Gram- positive bacteria. Therefore, since therapeutic selection for empirical treatment and management should be based on the knowledge of the local bacterial profile and antimicrobial response, we suggest physicians take this high resistance profile in to consideration when prescribing antimicrobials against the pathogens in question.
Engineered Butyrate-producing Bacillus Subtilis Alleviated Ethanol-induced Intestinal&nbsp;and Liver Damage in Mice
Authors: Lu Xing , Zhao Meiqi , Duan Yitao , Wang Fengmei , Chen Chuanai 
Published: November 2020

Abstract
Ethanol-induced intestinal and liver injury are closely associated with intestinal dysbiosis and altered short-chain fatty acid (SCFA) metabolites which is crucial for intestinal health. Bacillus subtilis (BS) strains with biotherapeutic potential can benefit the host through maintaining intestinal homeostasis and regulating systematic immunity via producing small molecules, although these molecules do not include butyrate. To combine the advantages of butyrate and BS, we evaluated the bioactivity of an engineered butyrate-producing Bacillus subtilis (BPBS) strain against ethanol exposure in a chronic-binge ethanol feeding mouse model. Our findings suggested that prophylactic BPBS supplementation restored eubiosis of the gut microbiota and intestinal barrier function, which obviously reduced bacterial translocation of microbial products especially lipopolysaccharide (LPS) to the circulatory system. Additionally, the decrease of serum LPS is responsible for the relief of hepatic inflammation via the Toll-like receptor 4 (TLR4) pathway, resulting in improved hepatic structure and function. Collectively, these results demonstrated that engineered BPBS intervention imparted novel hepatoprotective functions by improving intestinal barrier function and reducing systematic inflammation under ethanol exposure, as well as paving the way for further exploration of engineered probiotics in improving human health care.
MTDH Inhibits K48-Linked Degradation of TAK1 and Promotes Sorafenib Resistance in Hepatocellular Carcinoma
Authors: Xia Shunjie , Ji Lin , Wan Zhe , Pan Yu , Tao Liye , Lin Zhongjie , Pan Haoqi , Zhao Jie , Cai Liuxin , Xu Junjie , Cai XiuJun 
Published: November 2020

Abstract
BackgroundIdentifying novel and actional targets in hepatocellular carcinoma (HCC) remains an unmet medical need. TAK1 was originally identified as a TGF-β-activated kinase and was further proved to phosphorylate and activate numerous downstream targets and promote cancer progression. Although TAK1 depletion leads to early onset of hepatocarcinogenesis in mice, the role of TAK1 in developed HCC progression and targeted therapy resistance is poorly understood. MethodsThe expression of TAK1 and MTDH in HCC cell lines and patients and sorafenib-resistant models was analyzed by in silico analysis, quantitative real-time PCR, western blotting and immunohistochemistry. In vivo and In vitro experiments was introduced to examine the function of TAK1 or MTDH in HCC and sorafenib resistance using small interfering RNA and pharmacological inhibitors in combination with or without sorafenib. Co-immunoprecipitation and RNA immunoprecipitation was carried out to determine the binding between TAK1 and FBXW2 or between MTDH and FBXW2 RNA.ResultsOur findings unraveled the clinical significance of TAK1 in promoting HCC and sorafenib resistance. We identified a novel E3 ubiquitin ligase, FBXW2, targeting TAK1 for K48-linked polyubiquitylation and subsequent degradation. We also found that MTDH contributes to TAK1 upregulation in HCC and sorafenib resistance, through binding to FBXW2 mRNA and accelerate its degradation. Moreover, combination of TAK1 inhibitor and sorafenib suppressed the growth of sorafenib-resistant HCCLM3 xenograft in mouse models.ConclusionThese results revealed novel mechanism underlying TAK1 protein degradation and highlighted the therapeutic value of targeting TAK1 in suppressing HCC and overcoming sorafenib resistance.
Production, Purification and Characterization of Mannanase Obtained from Pichia Kudriavzevii Strain AUMC 10190 Isolated from Citrus Wastes
Authors: Afolabi Folake Titilayo , JIMOH YETUNDE ZAINAB 
Published: November 2020

Abstract
Microorganisms are now the main sources of industrial enzymes, with fungi and yeasts that have contributed about 50%, bacteria has contributed about 35%, whereas the remaining 15% are also of phytopathogenic fungi while some are plant parasitic nematodes or animal origin. The prospective of using these microorganisms as sources of biotechnological and industrial relevant enzymes motivated interest in the study of extracellular enzymes from numerous microorganisms which include various fungi, bacteria, actinomycetes and yeasts. The aim of this study was to isolate and screen for mannanase-producing yeasts from citrus wastes and to produce, optimize, purify and characterize the enzyme. One hundred and two (102) yeasts were isolated from different citrus wastes obtained from five different markets and screened for their mannanase producing ability. Gum Arabic was used as a substrate for the production of mannanase enzyme by yeasts isolates using submerged fermentation. Candida sp. LES2, Candida sp. OS12, Pichia sp. and Pichia kudriavzevii (AUMC 10190) were the yeast isolates with the best potential of mannanase production. Incubation period, pH, temperature, carbon and nitrogen source were optimized under submerged fermentation for the production of mannanase. The mannanase produced by Pichia kudriavzevii (AUMC 10190) was optimally active at pH 7.0 (202.10 U/ml) and its temperature is stable at 600C. Pichia kudriavzevii (AUMC 10190) was optimally active at 350C (147.91U/ml). Mannanase enzyme produced by Pichia kudriavzevii (AUMC 10190) had a purification fold of 2.14 with a specific activity of 134.53U/ml proving that yeasts obtained from citrus wastes have the ability to produce mannanase enzyme under optimized conditions. Therefore, it can be concluded that Pichia kudriavzevii (AUMC 10190) isolated from citrus waste is potential yeast for the production of mannanase under suitable condition for higher yield.
Quantifying productivity at landscape scale using remotely-sensed foliar traits and canopy structure
Authors: Wieczynski Daniel , Diaz Sandra , Duran Sandra M. , Fyllas Nikolaos , Salinas Norma , Martin Roberta , Shenkin Alexander , Silman Miles , Asner Gregory , Bentley Lisa P. , Malhi Yadvinder , Enquist Brian , Savage Van 
Published: November 2020

Abstract
Forests are integral to global carbon cycling but are threatened by anthropogenic degradation and climate change. Assessing this global threat has been hindered by a lack of clear, flexible, and easy-to-use productivity models along with a lack of functional trait and productivity data for parameterizing and testing those models. Current productivity models are either extremely complex requiring up to hundreds of parameters, many sub-models, and considerable computational expense or rely on statistical trait-growth relationships that can be hard to extrapolate to new systems or climates. Here we provide a simple alternative: a remote sensing canopy functional model (RS-CFM) that uses remotely-sensed foliar traits and canopy structure data to efficiently map productivity at high-resolution and large spatial scales. We test this model by quantifying net primary productivity (NPP) at 0.01-ha resolution in 30,040 hectares of Peruvian tropical rainforest along a 3,322-m Amazon-to-Andes elevation gradient. Our model predicts local NPP and elevational shifts in NPP much more accurately and in greater detail than a prominent alternative method—NASA’s MODIS NPP product. Furthermore, we show how NPP estimates depend on light competition and identify the appropriate spatial resolution for remote productivity estimation. Our framework opens up possibilities to fully harness remote sensing data and reliably scale up from traits to map regional or global productivity in a more direct, efficient, and cost-effective manner.
Understanding the Family Doctor Concept in Public Primary Care Clinics in Malaysia: Objectives, Initiatives, Resources, and Expected Outcomes
Authors: Ismail Aniza , Reffien Muhammad Alimin Mat , Sulong Saperi , Bahanuddin Tengku Putri Zaharah Tengku , Salleh Noridah Mohd , Nasir Nazrila Hairizan 
Published: November 2020

Abstract
IntroductionFamily Doctor Concept (FDC) was a program introduced at selected public primary care clinics to strengthen family practice in Malaysia. It is a healthcare delivery system approach that strives to achieve “One Family, One Doctor” concept so that the physicians can provide the population with comprehensive, continuous, collaborative, personal, family- and community-oriented services.Methods and materials We collected qualitative data collection via semi-structured interviews with stakeholders (Policymakers, healthcare providers, state- and clinic-level implementers). The data were analyzed using thematic analysis according to the Consolidated criteria for Reporting Qualitative Studies (COREQ) guideline for reporting the findings.ResultsThe 16 stakeholders who participated in this research agreed that the FDC is an approach to deliver integrated, personalized, family-centered, and comprehensive care to clients. However, there were other macro-level and longer-term objectives, such as mapping diseases and improving accessibility. FDC components were related to the objectives, and variation in the implementation was expected to suit different settings. Generally, the stakeholders disagreed on the input requirement, but all cited human resources as a significant limiting factor. There were numerous expected outcomes, which could be divided into short-, intermediate-, and long-term.ConclusionFDC consists of several change initiatives in a complex health care system whereby the capacity building of human resources is critical in achieving the desired outcomes. Thus, there is an urgent need for multiple stakeholders to reach common understanding and building a workable roadmap for successful implementation.
Knowledge of First aid in Nepalese School Students and Teachers.
Authors: Dahal Geha Raj , Vaidya Pradeep 
Published: November 2020

Abstract
BackgroundBasic knowledge on first aid is required to every citizen. School children are best target group for giving such training. School teachers have duel responsibility on this regard. They should have adequate knowledge on first aid so that they can provide when necessary and to train students. This study was conducted to assess the knowledge of school teachers and students and effect of first aid training. MethodsThis study was conducted in school teachers and high school students of 6 schools in Kathmandu. Two days training on first aid was given to all participants. Knowledge on first aid was assessed through self administered 10 questionnaires before and after training. Response was recorded as ‘correct’ or ‘incorrect’ of individual question and total score obtained by individual. Responses were compared before and after training and between students and teachers also. ResultsA total of 152 participants (121 students and 31 teachers) were included in the study. Average score in pretest and posttest was 5.1 ±1.56 and 8.01 ±1.49 respectively with P value 0.001. Majority were aware of meaning of first aid, time to perform CPR, and first aid knowledge on fracture and electric shock. First aid knowledge on other incidents was not satisfactory. The training improved overall knowledge of participants. There was no difference of knowledge in students and teachers. ConclusionFirst aid knowledge of school teachers and students was similar and not satisfactory. Training improves knowledge significantly.