bluuebunny/crossref_metadata_2025 huggingface dataset:
β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar
Authors: Ahmed Mazen A. Sid , Khan Faisal Ahmad , Sultan Ali A. , Soderquist Bo , Ibrahim Emad Bashir , Jass Jana , Omrani Ali S.
Published: October 2020

Background: The distribution of b-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD PhoenixTM system and manual Liofilchem MIC Test Strips. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.3%). All isolates possessed Class C and/or Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. High risk ST235 (n=16, 21.3%), ST357 (n=8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.
Knowledge, Attitudes and Understanding of Probiotics Among Pediatricians in Different Regions of Saudi Arabia
Authors: Hasosah Mohammed , Qurashi Mansour , Balkhair Abdullah , Alzahrani Ziyad , Alabbasi Abdullah , Alzahrani Muhanad , Alnahdi Wejdan , Shafei Sohaib , Bafaqih Malak , Khan Muhammad A
Published: October 2020

Background Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit upon the host. Knowledge and attitudes of health professionals have been reported to be at a medium level for probiotics . The objective was to evaluate the knowledge and practice styles about probiotics among pediatricians working in different regions of Saudi Arabia. Methods This cross-sectional study was conducted at pediatric hospitals in Saudi Arabia. A national survey of 550 pediatric providers (PPs) was conducted between January and March 2020 anonymously on their knowledge and practice styles regarding probiotics, and it was completed by pediatric residents (PRs), pediatric specialist (PSs), pediatric consultants (PCs), and pediatric gastroenterologists (PGs). Results The survey had a response rate of 82%. Among the respondents, 57.7% were aware of the probiotic’s definition. There were significant differences in the percentage of participants who had little knowledge of probiotics (P<0.05), with the highest being PRs and the lowest being PGs. The most common probiotic used by all participants was Lactobacillus acidophilus (63.3%), and Mycobacterium avium was prescribed the least often (8.6%). Most PRs and PSs correctly reported that probiotics reduce the risk of antibiotic-induced diarrhea (74.9% and 80.2%, respectively), but there were no significant differences among them. Conclusions Significant differences in knowledge and practice patterns exist for probiotics. Identification of knowledge gaps may be useful to develop educational materials to improve the proper definition, knowledge, and use of probiotics.
Single blinded semi-field evaluation of MAÏA® topical repellent ointment compared to unformulated 20% DEET against Anopheles gambiae, Anopheles arabiensis and Aedes aegypti in Tanzania
Authors: Mbuba Emmanuel , Odufuwa Olukayode , Tenywa Frank , Philipo Rose , Tambwe Mgeni , Swai Johnson Kyeba , Moore Jason , Moore Sarah
Published: October 2020

Background N, N-Diethyl-3-methylbenzamide (DEET) topical mosquito repellents are effective personal protection tools. However, DEET-based repellents tend to have low consumer acceptability because they are cosmetically unappealing. More attractive formulations are needed to encourage regular user compliance. This study evaluated the protective efficacy and protection duration of a new topical repellent ointment containing 15% DEET, MAÏA® compared to 20% DEET in ethanol using malaria and dengue mosquito vectors in Bagamoyo Tanzania.Methods Fully balanced 3x3 Latin square design studies were conducted in large semi-field chambers using laboratory strains of Anopheles gambiae sensu stricto, Anopheles arabiensis and Aedes aegypti. Human volunteers applied either MAÏA® ointment, 20% DEET or ethanol to their lower limbs six hours before the start of tests. Approximately 100 mosquitoes per strain per replicate were released inside each chamber, with 25 mosquitoes released at regular intervals during the collection period to maintain adequate biting pressure throughout the test. Volunteers recaptured mosquitoes landing on their lower limbs for six hours over a period of six to 12-hours post-application of repellents. Data analysis was conducted using mixed-effects logistic regression.Results The protective efficacy of MAÏA® and 20% DEET was not different for each of the mosquito strains: 95.9% vs 97.4% against An. gambiae (OR=1.53 [95% CI: 0.93–2.51] p=0.091); 96.8% vs 97.2% against An. arabiensis (OR =1.08 [95% CI: 0.66 –1.77] P=0.757); 93.1% vs 94.6% against Ae. aegypti (OR=0.76 [95% CI: 0.20-2.80] p=0.675). Average complete protection time (CPT) of MAÏA® and that of DEET was similar for each of the mosquito strains: 571.6 minutes (95% CI: 558.3-584.8) vs 575.0 minutes (95% CI: 562.1-587.9) against An. gambiae; 585.6 minutes (95% CI: 571.4-599.8) vs 580.9 minutes (95% CI: 571.1-590.7) against An. arabiensis; 444.1 minutes (95% CI: 401.8-486.5) vs 436.9 minutes (95% CI: 405.2-468.5) against Ae. aegypti.Conclusions MAÏA® repellent ointment provides complete protection for 9 hours against both An. gambiae and An. arabiensis, and 7 hours against Ae. aegypti similar to 20% DEET (in ethanol). MAÏA® repellent ointment can be recommended to be used as a tool for prevention of outdoor biting mosquitoes in tropical locations as it protects for more than 6 hours.
Genome-wide survey of sucrose non-fermenting 1-related protein kinase 2 in Rosaceae and expression analysis of PbrSnRK2 in response to ABA stress
Authors: Chen Guodong , Wang Jizhong , Qiao Xin , Jin Cong , Duan Weike , Sun Xiaochuan , Wu Juyou
Published: October 2020

Background: The members of the sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family are specific serine/threonine protein kinases in plants that play important roles in stress signal transduction and adaptation. Because of their positive regulatory roles in response to adverse conditions, the genes encoding thes proteins are considered potential candidates for breeding of plants for disease resistance and genetic improvement. However, there is far less information about this kinase family, and the function of these genes has not been explored in Rosaceae. Results: A genome-wide survey and analysis of the genes encoding members of the SnRK2 family were performed in pear ( Pyrus bretschneideri ) and seven other Rosaceae species. A total of 71 SnRK2 genes were identified from the eight Rosaceae species and classified into three subgroups based on phylogenetic analysis and structural characteristics. Purifying selection played a crucial role in the evolution of SnRK2 genes, and whole-genome duplication and dispersed duplication were the primary forces underlying the characteristics of the SnRK2 gene family in Rosaceae. Transcriptome data and qRT-PCR assay results revealed that the distribution of PbrSnRK2s was very extensive, including across the roots, leaves, pollen, styles, and flowers, although most of them were mainly expressed in leaves. In addition, under stress conditions, the transcript levels of some of the genes were upregulated in leaves in response to ABA treatment. Conclusions: This study provides useful information and a theoretical introduction for the study of the evolution, expression, and functions of the SnRK2 gene family in plants.
Longitudinal analysis of cell-free mutated KRAS and CA 19-9 predicts survival following curative resection of pancreatic cancer 
Authors: Hussung Saskia , Akhoundova Dilara , Hipp Julian , Follo Marie , Klar Rhena , Philipp Ulrike , Scherer Florian , von Bubnoff Nikolas , Duyster Justus , Börries Melanie , Wittel Uwe , Fritsch Ralph
Published: October 2020

Background: Novel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis of mutated cell-free plasma KRAS (cfKRASmut) and CA 19-9 during adjuvant treatment and follow-up might more accurately predict disease course than hitherto available parameters. Methods: Between 07/2015 and 10/2018, we collected 134 plasma samples from 25 patients after R0/R1-resection of PDAC during adjuvant chemotherapy and post-treatment surveillance at our institution. Highly sensitive discriminatory multi-target ddPCR assays were employed to screen plasma samples for cfKRASmut. cfKRASmut and CA 19-9 dynamics were correlated with recurrence-free survival (RFS) and overall survival (OS). Patients were followed-up until 01/2020.Results: Out of 25 enrolled patients, 76% had undergone R0 resection and 48% of resected PDACs were pN0. 17/25 (68%) of patients underwent adjuvant chemotherapy. Median follow-up was 22.0 months, with 19 out of 25 (76%) patients relapsing during study period. Median RFS was 10.0 months, median OS was 22.0 months. Out of clinicopathologic variables, only postoperative CA 19-9 levels and administration of adjuvant chemotherapy correlated with survival endpoints. cfKRASmut. was detected in 12/25 (48%) of patients, and detection of high levels inversely correlated with survival endpoint. Integration of cfKRASmut and CA 19-9 levels outperformed either individual marker. cfKRASmut outperformed CA 19-9 as dynamic marker since increase during adjuvant chemotherapy and follow-up was highly predictive of early relapse and poor OS. Conclusions: Integrated analysis of cfKRASmut and CA 19-9 levels is a promising approach for molecular monitoring of patients following resection of PDAC. Larger prospective studies are needed to further develop this approach and dissect each marker`s specific potential.
Using behavioral insights to design implementation strategies in public mental health settings: a qualitative study of clinical decision-making
Authors: Last Briana S , Schriger Simone H , Timon Carter E. , Frank Hannah E , Buttenheim Alison M. , Rudd Brittany N , Fernandez-Marcote Sara , Comeau Carrie , Shoyinka Sosunmolu , Beidas Rinad S.
Published: October 2020

Background: Trauma focused-cognitive behavioral therapy (TF-CBT) is an evidence-based intervention for youth with posttraumatic stress disorder. An important component of TF-CBT is the trauma narrative (TN), a phase in the intervention in which youth are guided to process the memories, thoughts, and feelings associated with their traumatic experience(s). Previous work has shown that only half of TF-CBT clinicians complete the TN with their clients. Drawing from the behavioral insights literature—an interdisciplinary field studying judgment and decision-making—the present study seeks to understand what determines clinician use of the TN and to generate strategies that target these determinants. Methods: Through semi-structured qualitative interviews, we sought the perspectives of trained TF-CBT clinicians working in public mental health settings across the city of Philadelphia (n=17) to understand their decisions to use the TN with clients. We analyzed the qualitative data using a coding approach informed by the behavioral insights literature. We used an iterative process of structured hypothesis generation, aided by a behavioral insights guide, and rapid validation informed by behavioral insights to uncover the determinants of TN use. We then generated implementation strategies that targeted these determinants using the “Easy Attractive Social Timely” framework, a behavioral insights design approach. Results: We generated and validated three broad themes about what determines clinician implementation of the TN: decision complexity, clinician affective experience, and agency norms. We hypothesized the behavioral insights that underlie these implementation determinants and generated a list of nine behavioral insights strategies that theoretically may facilitate TN implementation. Conclusions: Our study investigated why an effective component of an evidence-based intervention is difficult to implement. We leveraged robust scientific theories and empirical regularities from the behavioral insights literature to understand clinician perspectives on TN implementation. These factors were theoretically linked to implementation strategies. Our work revealed the potential for using behavioral insights in the diagnosis of evidence-based intervention determinants and the design of implementation strategies.
Handwashing and disinfection precautions taken by U.S. adults to prevent coronavirus disease 2019, Spring 2020
Authors: Brown Laura , Hoover E. Rickamer , Barrett Catherine , Esschert Kayla L. Vanden , Collier Sarah , Garcia-Williams Amanda
Published: October 2020

Objectives. The objectives of this study were to assess self-reported hygiene precautions taken by U.S. adults during spring 2020 to prevent coronavirus disease 2019 (COVID-19) and to identify demographic characteristics associated with these hygiene precautions. Results. We obtained data from Porter Novelli Public Services’s national survey, Spring ConsumerStyles, conducted March 19 – April 9, 2020 among a nationally representative random sample of 6,463 U.S. adults aged 18 years or older. We present data from the survey question: “What, if any, precautions are you taking to prevent coronavirus?”. Respondents replied yes or no to the following precautions: washing hands often with soap and water and disinfecting surfaces at home and work often. Most respondents reported taking hygiene-related precautions to prevent COVID-19; more respondents reported handwashing (93%) than disinfecting surfaces (74%). Men, younger respondents, those with lower income and education levels, and respondents in self-rated poor health had lower reported rates of both handwashing and disinfecting surfaces. Communications about hygiene precautions for COVID-19 prevention may need to target sub-populations with the greatest gaps in hygiene-related practices. Research identifying barriers to these practices and developing effective messaging could inform and improve these communications.
Ocular abnormalities in a large Western China patient cohort with Retinitis Pigmentosa
Authors: Tan Lian , Long Yanling , Li Ziyang , Ying Xi , Ren Jiayun , Sun Cheng , Meng Xiaohong , Li Shiying
Published: October 2020

Background To report the prevalence of ocular abnormalities and investigate visual acuity in a large Western China cohort of retinitis pigmentosa (RP) patients. Methods A retrospective study was performed, reviewing the medical records and ophthalmic examination reports of 2,127 eyes from 1,065 RP patients in one eye hospital. The authors investigated the prevalence of ocular abnormalities and the relationship between best corrected visual acuity (BCVA) and macular abnormalities. Results Nyctalopia (58.2%) and blurred vision (27.1%) were the leading consultation causes. BCVA measurements in the better eyes at first clinical presentation showed that 304 patients (28.5%) were categorised as blind and 220 patients (20.7%) as low vision. The most common ocular abnormalities were cataracts (43.1%) and macular abnormalities (59.7%), including epiretinal membranes (51.1%), cystoid macular edema (18.4%), vitreomacular traction syndrome (2.4%), macular holes (2.3%) and choroidal neovascular membranes (0.05%). Glaucoma was found in 35 eyes (1.6%). The proportions of epiretinal membranes (P=0.001) and macular holes (P=0.008) increased significantly with age. Cystoid macular edema was significantly associated with poorer visual acuity in RP patients with clear lens (P=0.002).Conclusion Cataracts and macular abnormalities are common in RP patients. In the macular abnormalities, cystoid macular edema may have a negative effect on BCVA in RP patients with clear lens. Therefore, OCT screening in RP patients is highly recommended for early detection and treatment of maculopathy.
Characterization of the Cytokinin sensor TCSv2 in Arabidopsis and Tomato
Authors: Steiner Evyatar , Israeli Alon , Gupta Rupali , Shwartz Ido , Nir Ido , Leibman-Markus Meirav , Tal Lior , Farber Mika , Amsalem Ziva , Ori Naomi , Muller Bruno , Bar Maya
Published: October 2020

Background: Hormones are crucial to plant life and development. Being able to follow the plants hormonal response to various stimuli and throughout developmental processes is an important and increasingly widespread tool. The phytohormone cytokinin (CK) has crucial roles in the regulation of plant growth and development. Results: Here we describe a version of the CK sensor Two Component signaling Sensor (TCS), referred to as TCSv2. TCSv2 has a different arrangement of binding motifs when compared to previous TCS versions, resulting in increased sensitivity in some examined tissues. Here, we examine the CK responsiveness and distribution pattern of TCSv2 in arabidopsis and tomato. Conclusions: the increased sensitivity and reported expression pattern of TCSv2 make it an ideal TCS version to study CK response in particular hosts, such as tomato, and particular tissues, such as leaves and flowers.
Relationships between test positivity rate, total laboratory confirmed cases of malaria, and malaria incidence in high burden settings of Uganda: An ecological analysis
Authors: Okiring Jaffer , Epstein Adrienne , Namuganga Jane F. , Kamya Victor , Sserwanga Asadu , Kapisi James , Ebong Chris , Kigozi Simon P. , Mpimbaza Arthur , Wanzira Humphrey , Briggs Jessica , Kamya Moses R. , Nankabirwa Joaniter I. , Dorsey Grant
Published: October 2020

Background: Malaria surveillance is critical for monitoring changes in malaria morbidity over time. National Malaria Control Programs often rely on surrogate measures of malaria incidence, including the test positivity rate (TPR) and total laboratory confirmed cases of malaria (TCM), to monitor trends in malaria morbidity. However, there are limited data on the accuracy of TPR and TCM for predicting temporal changes in malaria incidence, especially in high burden settings.Methods: This study leveraged data from 5 malaria reference centers (MRCs) located in high burden settings over a 15-month period from November 2018 through January 2020 as part of an enhanced health facility-based surveillance system established in Uganda. Individual level data were collected from all outpatients including demographics, laboratory test results, and village of residence. Estimates of malaria incidence were derived from catchment areas around the MRCs. Temporal relationships between monthly aggregate measures of TPR and TCM relative to estimates of malaria incidence were examined using linear and exponential regression models. Results: A total of 149,739 outpatient visits to the 5 MRCs were recorded. Overall, malaria was suspected in 73.4% of visits, 99.1% of patients with suspected malaria received a diagnostic test, and 69.7% of those tested for malaria were positive. Temporal correlations between monthly measures of TPR and malaria incidence using linear and exponential regression models were relatively poor, with small changes in TPR frequently associated with large changes in malaria incidence. Linear regression models of temporal changes in TCM provided the most parsimonious and accurate predictor of changes in malaria incidence, with adjusted R2 values ranging from 0.81 to 0.98 across the 5 MRCs. However, the slope of the regression lines indicating the change in malaria incidence per unit change in TCM varied from 0.57 to 2.13 across the 5 MRCs, and when combining data across all 5 sites, the R2 value reduced to 0.38. Conclusions: In high malaria burden areas of Uganda, site-specific temporal changes in TCM had a strong linear relationship with malaria incidence and were a more useful metric than TPR. However, caution should be taken when comparing changes in TCM across sites.
Polyaniline Nanoskein: Synthetic Method, Characterization, and Redox Sensing
Authors: Hong Yoochan , Kim Hyun Soo , Lee Taeha , Lee Gyudo , Kwon Ohwon
Published: October 2020

Polyaniline nanoskein (PANS), which have polyaniline nanofibers, is developed. PANS is formulated via sequential extracting, heating, and swelling processes. The compositions of PANS have been analyzed using X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and Brunauer-Emmett-Teller analysis, and the results of which indicate that PANS is composed of solely organic materials. Moreover, PANS have been shown convertible absorbance characteristics according to surrounding acidic environments, and using these characteristics, the possibility of PANS for sensing of surrounding redox states changes is presented.
Correlation analysis of MTHFD1 gene polymorphisms and neural tube defects in Han population of Northern China
Authors: Fang Yulian , Liu Yan , Shu Jian-Bo , Zhao Lin-Sheng , Wang Lu , Wang Xue-Tao , Zhi Xiu-Fang , Zheng Jie , Shi Ou-Yan , Cai Chun-Quan
Published: October 2020

Background
Neural tube defects (NTDs) is a common birth defects worldwide. The methylenetetrahydrofolate dehydrogenase1 (MTHFD1) gene has been proved to play an important role in folate metabolism, which was strongly associated with the increased NTDs risk. The study is aimed to explore the correlation of single nucleotide polymorphisms (SNPs) in MTHFD1 gene with NTDs susceptibility.
Methods
A case-control study was conducted on children who included 152 NTDs patients and 169 healthy controls. Tag-SNPs were identified in HapMap database. Then, we investigated the association between NTDs and four selected tag-SNPs in MTHFD1 gene: rs1950902, rs2236225, rs2236224, rs11849530. We also performed a meta-analysis based on previous published studies to further evaluate the association.
Results
The results indicated that rs2236225 polymorphism displayed a significant association with NTDs risk (AA vs. GG: OR = 2.862, 95%CI = 1.022ཞ8.015; GA + AA vs. GG: OR = 1.619, 95%CI = 1.040ཞ2.520; A vs. G: OR = 1.500, 95%CI = 1.061ཞ2.120). In addition, rs2236224 polymorphism was correlated with increased NTDs risk (TT vs. CC: OR = 2.559, 95%CI = 1.128ཞ5.804; CT + TT vs. CC; OR = 1.631, 95%CI = 1.041ཞ2.556; T vs C: OR = 1.489, 95%CI = 1.072ཞ2.068). Further analysis showed the harmful effect of rs2236225 polymorphism was further supported by the result of meta-analysis. Meanwhile, haplotype analysis results showed that A-A and T-A haplotypes were correlated with increased NTDs risk, but C-A haplotype might decrease NTDs risk.
Conclusions
The results indicated that rs2236225 and rs2236224 polymorphisms of MTHFD1 gene were significantly associated with NTDs susceptibility in Han population of Northern China.
Pollution Control for Nature Surface Water 
Authors: Fakron Malik
Published: October 2020

The huge amounts of pollutants in nature surface water in. This contaminates due to different operations in surface water. During the past fifty years, increasing attention has centered on the discharge of sewage into coastal waters. This practice has been widely criticized on the grounds that sewage-polluted seawater is a health hazard to bathers. The pollution of the surface water is becoming more and more serious. The marine environment has undergone great changes. This research is presented two methods to control pollution and rehabilitation environment. First method by using temporary floating a waterfall for removing containment from the surface water and reducing concentration total suspended matter in surface water and reducing concentrations for phosphate, nitrogen, organic carbon. Second method by using towed rotating biological contactors to reducing concentrations for phosphate, nitrogen, and organic carbon. To control effects of algae bloom occurs. These two methods are converted to heterogeneous reactor with solid catalysts; this reactor is multi step treatment. First step is screening and second step is solid catalyst bed reactor. As waterfall or towed rotating biological contactor is multi bed reactor. The water quality assessment for selection best scheme for enhancement water quality for surface water is based on acceptable japan environmental ministry guidelines for surface water quality level for bathing.
Substrate-biased activity-based probes identify the urokinase-plasminogen axis as a master regulator of metastatic signaling by orphan membrane receptor CDCP1
Authors: Kryza Thomas , Khan Tashbib , Lovell Scott , Harrington Brittney S. , Yin Julia , Porazinski Sean , Pajic Marina , Koistinen Hannu , Rantala Juha , Dreyer Tobias , Magdolen Viktor , Reuning Ute , He Yaowu , Tate Edward , Hooper John David
Published: October 2020

CDCP1 is an oncogenic orphan transmembrane receptor and a promising target for detection and treatment of cancer. Extracellular proteolysis of CDCP1 by poorly defined mechanisms induces pro-metastatic signaling. We describe a novel approach for rapid identification of proteases responsible for key proteolytic events exploiting a substrate-biased activity-based probe (sbABP) that incorporates a substrate cleavage motif grafted onto a peptidyl-diphenyl-phosphonate warhead for specific target protease capture, isolation and identification. Using a CDCP1-biased probe we identify urokinase (uPA) as the master regulator of CDCP1 proteolysis, both by direct cleavage and via activation of CDCP1-cleaving plasmin. We show that co-expression of uPA and CDCP1 is strongly predictive of poor disease outcome across multiple cancers and demonstrate that uPA-mediated CDCP1 proteolysis promotes metastasis in disease-relevant preclinical in vivo models. These results highlight CDCP1 cleavage as a potential target to disrupt cancer and establish sbABP technology as a new approach to identify disease-relevant proteases.
Spatial transcriptome sequencing of FFPE tissues at cellular level
Authors: Liu Yang , Enninful Archibald , Deng Yanxiang , Fan Rong
Published: October 2020

Formalin-fixed paraffin-embedded (FFPE) tissues are the most abundant archivable specimens in clinical tissue banks, but unfortunately incompatible with single-cell level whole transcriptome sequencing due to RNA degradation in storage and RNA damage in extraction. We developed an in-tissue barcoding approach namely DBiT-seq for spatially revolved whole transcriptome sequencing at cellular level, which required no tissue dissociation or RNA exaction, thus potentially more suited for FFPE samples. Herein, we demonstrated spatial transcriptome sequencing of embryonic and adult mouse FFPE tissue sections at cellular level (25µm pixel size) with high coverage (>1,000 genes per pixel). Spatial transcriptome of an E10.5 mouse embryo identified all major anatomical features in the brain and abdominal region. Integration with single-cell RNA-seq data for cell type identification indicated that most tissue pixels were dominated by single-cell transcriptional phenotype. Spatial mapping of adult mouse aorta, atrium, and ventricle tissues identified the spatial distribution of a variety of cell types. Spatial transcriptome sequencing of FFPE samples at cellular level may provide enormous opportunities in a wide range of biomedical research. It may allow us to exploit the huge resource of clinical tissue specimens to study human disease mechanisms and discover tissue biomarkers or therapeutic targets
The conserved core component EsaA mediates bacterial killing by the type VIIb secretion system
Authors: Mietrach Nicole , Damián-Aparicio Diana , Isupov Michail , Krupka Marcin , Lopez Daniel , Geibel Sebastian
Published: October 2020

Type VII secretion systems (T7SS) are employed by Gram-positive bacteria to infect the host or to intoxicate bacterial competitors. Bacterial killing mediated by other secretion systems involves the assembly of large, extracellular structures promoting toxin delivery into bacterial competitors. However, such extracellular structures are not known for T7SS nor is it known whether the secreted toxins have cell-penetrating properties. Here, we used a multi-drug resistant Staphylococcus aureus, one of the most relevant hospital-associated bacterial pathogens, to study the mechanism of bacterial killing by the T7SSb. We report the proteolytic resistant, extracellular structure of the EsaA core component, which is an integral part of the membrane-embedded T7SSb secretion machine. The extracellular structure of EsaA has an elongated antenna-like shape providing an explanation how the T7SSb spans the staphylococcal cell wall. We demonstrate that the extracellular structure of EsaA has an essential function in secretion and contributes to the killing of prey bacteria. We show that the bactericidal activity of EsaA can be attributed to a membrane-damaging activity that leads to the permeabilization of phospholipid bilayers and could facilitate the delivery of antibacterial toxin into bacterial competitors. The structural similarity of the EsaA tip domain to bacterial lectins and human integrins suggests an additional function of EsaA in cell adhesion during infection or in targeting of bacterial competitors.
Structural Characteristics and Functional Analysis of Gut Microbiome in Patients with Osteoarthritis
Authors: Xie Zheng , Pi Guofu , Xu Zhiming , Li Chengxiang , Sun Xing , Chen Yangyang , Li Feng
Published: October 2020

ObjectiveRecent studies illustrated that changes of gut microbiome in human body may be related to the pathogenesis of osteoarthritis (OA). We aimed to determine the difference of gut microbiome between patients with osteoarthritis and normal people.MethodsThe samples were collected from 56 patients with osteoarthritis (34 females) and 52 healthy subjects (28 females). High-throughput sequencing of 16S rRNA gene was used to analyze the classification and composition of gut microbiome in OA patients, and then we used Linear discriminant analysis Effect Size (LEfSe) to find out the main differential bacteria and biomarkers in OA patients. At last, PICRUSt was applied to predict the genomic function of gut microbiome in OA patients, and we explored its mechanism in the development of the OA.ResultsThe association between gut microbiome and osteoarthritis has not been demonstrated in detail. Herein, we investigated the gut microbiome of OA patients and its relationship with the disease to evaluate the potential of the gut microbiome in the diagnosis and treatment of osteoarthritis. And we identified that there are significant differences in the β diversity of the gut microbial composition between the control group and OA patients (p＜0.05, respectively), and Bifidobacterium, Faecalibacterium and Alistipes have the potential to become biomarkers of osteoarthritis. Besides, the genomes of gut microbiome in OA patients are enriched in metabolic pathways and lipopolysaccharide biosynthesis (p=0.049, p=0.005), but in signal pathways related to apoptosis, the degree of enrichment was significantly higher than that of healthy people (p=0.006).ConclusionOur research identified that the community composition of gut microbiome in OA patients was different from that in normal groups and explored the role of gut microbiome in the development of osteoarthritis, which may provide a new theoretical basis for the study of osteoarthritis.
Diagnostic value of bronchoalveolar lavage-fluid soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) concentration for neonatal ventilator-associated pneumonia
Authors: Zhou Jian , Zhou Jingqian , Hong Yan , Wang Youcheng , Lin Hailong , Huang Leting
Published: October 2020

Background: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) has regarded as a biological marker of infection.We aimed to evaluate the diagnostic value of bronchoalveolar lavage (BAL)-sTREM-1 concentration in neonatal ventilator-associated pneumonia (NVAP).Methods: In this multicenter, controlled clinical trial of 60 preterm and 33 full-term neonates on mechanical ventilators, we measured concentrations of BAL-fluid and serum sTREM-1, serum C-reactive protein, and serum procalcitonin, as well as white blood cell count. We initially divided cases into eight groups, based on three categories: preterm of full-term; NVAP or non-NVAP; and extrapulmonary infection present or absent. Groups were compared, and logistic regression analysis and receiver operating characteristic (ROC) analysis was performed to determine diagnostic value.Results: The mean gestational age (± standard deviation) of preterm and full-term neonates was 28.9±2.2 weeks and 39.5±1.7 weeks, respectively, and 32/60 were male. The BAL-fluid sTREM-1 concentration was higher in NVAP cases than in non-NVAP cases, irrespective of extrapulmonary infection. ROC analysis revealed that BAL-fluid sTREM-1 concentration had an area under the curve (AUC) of 0.986 and a cutoff value of 228.0 pg/ml (sensitivity, 94.3%; specificity, 96%) in preterm neonates; the same values in full-term neonates were 0.938 and 245.5 pg/ml (sensitivity, 100%; specificity, 93.7%), respectively. The optimal combination of indicators was BAL-fluid sTREM-1 and serum C-reactive protein concentration. All indicators were present at lower levels on days 8 and 10 of ventilation in neonates who ultimately recovered than in those who did not. Conclusions: BAL-fluid sTREM-1 and serum C-reactive protein concentrations may be useful for the diagnosis of NVAP.Blinded manuscript textThe RCT was approved by the Ethics Review Committee ofThe First People's Hospital of Yongkang (number: ykyy201803). Furthermore, the study was registered in and approved by the Registration Centre of Clinical Trials in China (approval number: ChiCTR1900020564). URL of trial registry record:http://www.chictr.org.cn/showproj.aspx?proj=22336 Date of registration:2017-10-19
Assessment of health workers’ concern about COVID-19 pandemic: implication for surveillance activities among Primary Health Care workers in Oyo State, South-Western Nigeria
Authors: Babatunde Olaniyan Akintunde , Olatunji Muideen Babatunde , Akande Roseline Oluyemisi , Olumoyegun Joseph Muyiwa
Published: October 2020

Background: The outbreak of COVID-19 has continued to threaten the existence of human race. The novelty and unstable epidemiologic pattern of the virus had generated so much concern among the global health experts. These concerns were found to be escalated among frontline health care workers to the extent of impeding the timeliness of the response activities. To slow down the spread of the already established community transmission through the surveillance activities, the concern of the health workers at the community level needs to be addressed. Therefore, this study assessed the concern about COVID-19 pandemic among the primary health workers in Oyo State, Nigeria.MethodsThis was an online cross-sectional survey conducted among primary health care workers in Oyo State between March and April 2020. Using a two-stage sampling technique, we recruited 284 respondents. A semi-structured questionnaire linked to the Google form was used to collect data. Data were analyzed using IBM SPSS version 25; bivariate analysis was done using Chi-square and binary logistic regression was used to identify the predictors of health workers’ concern at 5% level of significance.ResultsThe mean age of respondents was 45.0 + 9.0 years. About 52.5% had goodk knowledge of COVID-19. In the domains of concern, 66.9%, 53.2%, 51.4%, and 46.5% of the respondents expressed government-related concern, self-satisfaction related concern, work-related concern and social status related concern respectively. Male respondents were less likely to express concern about COVID-19 compared with their female counterparts (aOR= 0.39, 95% CI = 0.20 – 0.76). Nurses/midwives (aOR= 0.21, 95% CI = 0.05 – 0.85) had lesser likelihood of expressing concern about COVID-19 while middle staff (aOR= 2.5, 95% CI = 1.18 – 5.39) and income earner of ≥ N200, 000 (aOR= 2.3, 95% CI = 1.34 – 3.92) had higher likelihood of expressing concern about COVID-19.ConclusionThe study revealed an average knowledge of COVID-19 among the respondents. Government-related and self-satisfaction related concerns were majorly expressed by the majority of the PHC workers. Therefore, holistic policy that addresses the welfare and training of the HCWs is recommended.
Muon-catalyzed fusion and annihilation energy generation supersede non-sustainable T+D nuclear fusion
Authors: Holmlid Leif
Published: October 2020

Background: Large-scale fusion reactors using hydrogen isotopes as fuel are still under development at several places in the world. These types of fusion reactors use tritium as fuel for the T +D reaction. However, tritium is not a sustainable fuel to use, since it will require fission reactors for its production, and since it is a dangerous material due to its radioactivity. Thus, fusion relying on tritium fuel should be avoided, and at least two better methods for providing the nuclear energy needed in the world indeed exist already. The first experiments with sustained laser-driven fusion above break-even using deuterium as fuel were published already in 2015.Results: The well-known muon-induced fusion (also called muon-catalyzed fusion) can use deuterium as fuel. With the recent development of a high intensity (patented) muon source, this method is technically and economically feasible today. The recently developed annihilation energy generation uses ordinary hydrogen as fuel. Conclusions: muon-induced fusion is able to directly replace most combustion-based power stations in the world, giving sustainable and environmentally harmless power (primarily heat), in this way eliminating most CO2 emissions of human energy generation origin. Annihilation-based power generation has the potential to replace almost all other uses of fossil fuels within a few decades, also in most mobile applications including spaceflight, where it is the only method which gives relativistic rocket propulsion.
Blood Virosphere in Febrile Tanzanian Children
Authors: Cordey Samuel , Laubscher Florian , Hartley Mary-Anne , Junier Thomas , Keitel Kristina , Docquier Mylène , Guex Nicolas , Iseli Christian , Vieille Gael , Mercier Philippe Le , Gleizes Anne , Samaka Josephine , Mlaganile Tarsis , Kagoro Frank , Masimba John , Said Zamzam , Temba Hosiana , Tapparel Caroline , Zanella Marie-Celine , Xenarios Ioannis , Fellay Jacques , D’Acremont Valérie , Kaiser Laurent
Published: October 2020

Background: Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Untargeted metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Results: Here, we describe the blood virome of 816 febrile children (<5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half the population (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens.Conclusions: This study highlighted several DNA and RNA viral sequences on a population of young children with fever of unknown origin and/or severe outcomes living in Tanzania, and provides a large list of novel viruses that should be considered as a potential cause of human infections.
COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia
Authors: Chauhan Garima , Kumar Gaurav , Roy Koustav , Kumari Punita , Alam Shahnawaz , Thondala Bhanuteja , Kishore Krishna , Panjwani Usha , Ray Koushik
Published: October 2020

BackgroundLow oxygen environments like hypobaric hypoxia (HH) are common nodes to various diseases: characterized by neuroinflammation, which is detrimental to the structural and functional aspects of hippocampal circuitry. Various hypoxic conditions also lead to elevation of NLRP3 mediated neuroinflammation that may contribute to cognitive deficits. Components of neurogenic niches like microglia and astrocyte are largely affected by neuroinflammation; however, a systematic investigation of the impact of NLRP3 mediated neuroinflammation on components of neurogenic niche during hypoxia (HH) remains elusive. MethodsIn this study, we simulated cerebral hypoxia via decreasing partial pressure of oxygen(HH). The effect of hypobaric hypoxic (1, 3 and 7 day at 25000 ft) on social memory, anxiety, adult neurogenesis change in the inflammatory milieu in DG was explored in detail. We explored the efficacy of COX-1 inhibitor (Valery salicylate, 5mg/kg/day,i.p), and EP1R antagonist (SC19220, 1mg/kg/day,i.p) on NLRP3 mediated neuroinflammation and associated maladies during HH. ResultsWe observed that HH exposure induced alteration in social and anxiety-like behavior post 7 day exposure along with perturbation in levels of BDNF, Serotonin and adult neurogenesis in the DG right from day 1. Moreover, significant elevated NLRP3, caspase-1, and IL-1β levels are observed during HH from day 1. Concomitantly, a notable increase in the COX-1/EP1 pathway in both activated microglia and astrocyte in DG was evident after 3HH exposure. Pharmacological COX-1 inhibitor and EP1 antagonist counteract the detrimental effects of HH exposure on social memory, adult neurogenesis, and NLRP3 inflammasome induction. ConclusionsThus, our data showed induction of the COX-1/EP1 pathway in glial cells is detrimental to adult neurogenesis and social memory, raising possibility that the COX-1/EP1 pathway as a plausible target for inflammasome related neurogenesis impairment.
WITHDRAWN: The Prevalence of Depression and Its Association With Quality of Life Among Pregnant and Postnatal Women in China: A Multicenter Study
Authors: Bo Haixin , YANG YUAN , Zhang Dongying , Zhang Meng , Wang Peihong , Liu Xiaohua , Ge Lina , Lin Wenxuan , Xu Yang , Zhang Yalan , Li Fengjuan , Xu Xujuan , Wu Honghe , Jackson Todd , Ungvari Gabor S , Cheung Teris , Xiang Yutao
Published: October 2020

Background: This study examined the prevalence of depressive symptoms (depression hereafter) and its association with quality of life (QOL) among pregnant and postnatal women in China.Methods: In this multicenter, cross-sectional study, 1,060 pregnant and postnatal women from eight hospitals were assessed. Depression and QOL were measured using standardized instruments.Results: The prevalence of depression was 7.45% (95%CI: 5.87%-9.04%) in the sample. Women with depression had lower QOL in physical, psychological, social and environmental domains compared to those without. Women with physical comorbidities were more likely to suffer from depression (OR=2.391, 95%CI=1.384-4.130, P=0.002).Conclusion: Due to its negative association with QOL, increased attention should be paid to depression in pregnant and postnatal women. Regular screening assessment and preventive measures should be adopted to reduce risk of depression in this population.
Comparable Obesity Parameters with Lung Function in A Chinese Rural Adult Population
Authors: Zeng Xiang , Liu Dongling , An Zhen , Li Huijun , Song Jie , Li Juan , Li Yuchun , Jiang Jing , Li Wen , Gui Lihui , Wu Weidong
Published: October 2020

Background: To assess association between diﬀerent obesity parameters and lung function indicators in a Chinese rural adult population. Methods: A total of 8,284 Chinese adults aged 20 to 80 years old from Xinxiang were recruited in this study. Obesity parameters including BMI, waist circumference (WC), hip circumference (HC), waist hip ratio (WHR), waist height ratio (WHtR), body fat percentage (BFP), basal metabolism (BM), and visceral fat index (VFI) and lung function parameters such as forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured according to previous guidance.Results: The total prevalence of obesity defined by BMI, WL, WHR, WHtR, and BFP were 23.2%, 58.2%, 66.7%, 69.2%, and 56.5%. In general, the prevalence of obesity in women was higher than that in men. The average levels of FVC and FEV1 in participants were 3.19 ± 0.72 (L) and 2.68 ± 0.64 (L), respectively. Men have a higher lung function levels than that of women. Lung function levels in obesity group were lower than those in non-obesity group, regardless of gender. Spearman correlation analyses showed that obesity parameters including BMI, WC, HC, WHR, WHtR, BFP, BM, and VFI were significantly correlated with lung function levels such as FVC and FEV1. After adjustment for the potential confounders in further linear regression analyses, BMI, WHtR, BFP, and obesity defined by BMI, WHtR and BFP were negatively associated with lung function, while WC, WHR, and obesity defined by WC and WHR were positively associated with lung function.Conclusions: Taken together, obesity status is closely related to lung function in general Chinese adult population. Weight control and lose is an important strategy to improve of lung function and reduce incidence of respiratory diseases.
CDK1/FBXW7 Facilitates Degradation and Ubiquitination of MLST8 to Inhibit Progression of Renal Cell Carcinoma
Authors: Zhang Encheng , Dong Xiao , Shao Jialiang , Mu Xingyu , Chen Siteng , Wang Yuqi , Zhang Pingzhao , Tan mingyue , Shi Qing , Wang Xiang
Published: October 2020

Background: Recent studies have reported that MLST8 is upregulated in many malignant tumors. Nevertheless, the underlying molecular mechanisms is still unclear. The aim of this work was to investigate how MLST8 contribute to the development and progression of renal cancer (ccRCC).Methods: To identify molecular mediators of the oncogenic tumor function of MLST8, we analyzed a quantitative mass spectrometry by a previous study and checked the amino acid sequence in MLST8. Immunoprecipitation and Western Blotting were used to analyze the interaction between FBXW7 and MLST8. Transwell assays determined cell migration and invasion. In vivo experiments were performed to verify tumor growth. Immunohistochemistry was used to analyze protein levels in patients’ tumor samples. Results: MLST8 is an oncogenic protein in TCGA database and ccRCC clinical specimens. We also ascertain that MLST8 interacts with FBXW7, which was universally regarded as an E3 ubiquitin ligase. MLST8 can be degraded and ubiquitinated by tumor suppressor FBXW7. FBXW7 recognizes a consensus motif (T/S) PXX (S/T/D/E) of MLST8 and triggers MLST8 degradation via the ubiquitin-proteasome pathway. Strikingly, the activated CDK1 kinase engages in the MLST8 phosphorylation required for FBXW7-mediated degradation. In vitro and vivo assay, we further prove that MLST8 is an essential mediator of FBXW7 inactivation-induced tumor growth, migration, and invasion. Furthermore, MLST8 and FBXW7 protein are negatively correlated in human renal cancer specimens. Conclusions: Our findings suggest that MLST8 is a putative oncogene that functions via interaction with FBXW7, and inhibition MLST8 can be a potential future target in ccRCC treatment.