bluuebunny/crossref_metadata_2025 huggingface dataset:
1-Methyl-D-tryptophan activates aryl hydrocarbon receptor, a pathway associated with bladder cancer progression
Authors: Matheus Luiz Henrique Gomes , Dalmazzo Stephanie Vanin , Brito Rodrigo Barbosa Oliveira , Pereira Lucas Alves , Almeida Robson José , Camacho Cleber Pinto , Dellê Humberto
Published: September 2020

Background: Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising target for immunotherapy in bladder cancer (BC). IDO1 breaks-down tryptophan to generate kynurenine derivatives, which may activate the aryl hydrocarbon receptor (AHR). AHR is an important target for carcinogens, but its association with BC progression was unknown. Two IDO1 inhibitors used in clinical trials are 1-methyl-D-tryptophan (MT) and INCB240360. Because MT is an aromatic hydrocarbon, it may be a ligand for AHR. We hypothesized that AHR could be associated with BC progression and that MT could activate AHR in BC.Methods: BC patients (n=165) were selected from the Gene Expression Omnibus database. A cut-off point for relative expression of AHR and cytochrome 450 enzymes (CYP1A1, CYP1A2, and CYP1B1; markers of AHR activation) was determined to compare with the grade, stage, and tumor progression. For in vitro experiments, RT4 (grade 1) and T24 (grade 3) BC cells were incubated with MT and INCB240360 to evaluate the expression of AHR and CYP1A1.Results: AHR activation was associated with grade, stage, and progression of BC. T24 cells express more CYP1A1 than RT4 cells. Although IDO1 expression and kynurenine production are elevated in T24 cells concomitantly to CYP1A1 expression, IDO1 inhibitors were not able to decrease CYP1A1 expression, in contrast, MT significantly increased it in both cell lines.Conclusion: In conclusion, it is rational to inhibit IDO1 in BC, among other factors because it contributes to AHR activation. However, MT needs to be carefully evaluated for BC because it is an AHR pathway agonist independently of its effects on IDO1.
Molecular epidemiology of a fatal sarcoptic mange epidemic in endangered San Joaquin kit foxes (Vulpes macrotis mutica)
Authors: Rudd Jaime L. , Clifford Deana L. , Cypher Brian L. , Hull Joshua M. , Riner A. Jane , Foley Janet E.
Published: September 2020

Background: In 2013, sarcoptic mange, caused by Sarcoptes scabiei mites, precipitated a catastrophic decline of the formerly stable urban population of endangered San Joaquin kit foxes (Vulpes macrotis mutica) in Bakersfield, California, USA. In 2019, a smaller sarcoptic mange outbreak affected kit foxes 58 km southwest of Bakersfield in the town of Taft, California. To determine whether the Taft outbreak could have occurred as spillover from the Bakersfield outbreak and whether epidemic control efforts must involve not only kit foxes but also sympatric dogs (Canis lupus familiaris), coyotes (Canis latrans), and red foxes (Vulpes vulpes), we evaluated genotypes and gene flow among mites collected from each host species. Methods: We used 10 Sarcoptes microsatellite markers (SARM) to perform molecular typing of 445 S. scabiei mites collected from skin scrapings from twenty-two infested kit foxes, two dogs, five coyotes, and five red foxes from Bakersfield, Taft, and other nearby cities. Results: We identified 60 alleles across all SARM loci; kit fox- and red fox-derived mites were relatively monomorphic, while genetic variability was greatest in Bakersfield coyote- and dog-derived mites. AMOVA analysis documented distinct mite populations unique to hosts, with an overall FST of 0.467. The lowest FST (i.e. closest genetic relationship, FST = 0.038) was between Bakersfield and Taft kit fox-derived mites while the largest genetic difference was between Ventura coyote- and Taft kit fox-derived mites (FST = 0.843). Conclusions: These results confirm the close relationship between the Taft and Bakersfield outbreaks. Although a spillover event likely initiated the kit fox mange outbreak, mite transmission is now primarily kit fox-to-kit fox. Therefore, any large-scale population level intervention should focus on treating kit foxes within the city.
IL6/sIL6R Regulates Tnfa-Inflammatory Response in Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms
Authors: Valin Alvaro , Rey Manuel J. Del , Municio Cristina , Usategui Alicia , Romero Marina , Fernández-Felipe Jesús , Cañete Juan D. , Blanco Francisco J. , Ruano Yolanda , Criado Gabriel , Pablos José L.
Published: September 2020

Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF.Methods: SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value <0.05 was considered statistically significant.Results: The stimulation of SF with IL6/sIL6R and TNFa, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions: These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.
High sensitivity of one-step real-time reverse transcription quantitative PCR to detect low virus titers in large mosquito pools
Authors: Tang Zhaoyang , Yamada Hanano , Kraupa Carina , Canic Sumejja , Busquets Núria , Talavera Sandra , Jiolle Davy , Vreysen Marc J. B. , Bouyer Jérémy , Abd-Alla Adly
Published: September 2020

Background: Mosquitoes are the deadliest animals in the world. Their ability to carry and spread diseases to humans causes millions of deaths every year. Due to the lack of efficient vaccines, the control of mosquito-borne diseases primarily relies on the management of the vector. Traditional control methods are insufficient to control mosquito populations. The sterile insect technique (SIT) is an additional control method that can be combined with other control tactics to suppress specific mosquito populations. The SIT requires the mass-rearing and release of sterile males with the aim to induce sterility in the wild female population. Samples collected from the environment for laboratory colonization, as well as the released males, should be free from mosquito-borne viruses (MBV). Therefore, efficient detection methods with defined detection limits for MBV are required. Although a one-step reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) method was developed to detect arboviruses in human and mosquito samples, its detection limit in mosquito samples has yet to be defined. Methods: We evaluated the detection sensitivity of one step RT-qPCR for targeted arboviruses in large mosquito pools, using pools of non-infected mosquitoes of various sizes (165, 320 and 1600 mosquitoes) containing one infected mosquito body with defined virus titers of chikungunya virus (CHIKV), usutu virus (USUV), West Nile virus (WNV) and Zika virus (ZIKV).Results: CHIK, USUV, ZIKV, and WNV virus were detected in all tested pools using the RT-qPCR assay. Moreover, in the largest mosquito pools (1600 mosquitoes), RT-qPCR was able to detect the targeted viruses using different total RNA quantities (10, 1 and 0.1 ng per reaction) as a template. Correlating the virus titer with the total RNA quantity allowed the prediction of the maximum number of mosquitoes per pool in which the RT-qPCR can theoretically detect the virus infection.Conclusions: Mosquito-borne viruses can be reliably detected by RT-qPCR assay in pools of mosquitoes exceeding 1000 specimens. This will represent an important step to expand pathogen-free colonies for mass-rearing sterile males for programmes that have a SIT component by reducing the time and the manpower needed to conduct this quality control process.
Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis
Authors: Santana Monique FM , Lira Aécio LA , Pinto Raphael , Minanni Carlos A , Silva Amanda RM , Sawada Maria IBAC , Nakandakare Edna R , Correa-Giannella Maria LC , Queiroz Marcia S , Ronsein Graziella E , Passarelli Marisa
Published: September 2020

Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: Individuals with DKD were divided into eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR<60+A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR<60+A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove 14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR<60+A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. Conclusion: The increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.
Maternal syphilis treatment and pregnancy outcomes: a retrospective study in Jiangxi Province, China
Authors: Wan Zhihua , Zhang Huan , Xu Haigang , Hu Yang , Tan Cai , Tao Yuling
Published: September 2020

Background: Studies investigating the associations of maternal syphilis treatment with birth outcomes mainly concentrated in economically developed areas. Limited data are available in economically underdeveloped areas, such as Jiangxi Province. The study aims to investigate the impact of maternal treatment on birth outcomes in Jiangxi Province, China.Methods: Data were obtained from the China’s Information System of Prevention of Mother-to-Child Transmission in Jiangxi Province. All syphilis infected pregnant women who delivered ≥28 gestational weeks and were registered in this system between 1 January 2013 and 31 December 2019 were enrolled. Pregnancy outcomes were evaluated by group-specific analyses according to their treatment status, adequacy and initiation time.Results: 4210 syphilis infected pregnant women were included in the analyses. Infants born to untreated mothers (n = 1364) were at significantly higher risk for stillbirth (adjusted odds ratio (aOR) = 1.74, 95% CI, 1.01-3.00, P = 0.045), preterm birth (aOR = 1.27, 95% CI, 1.02-1.59, P = 0.034) and low birth weight (LBW) (aOR = 1.44; 95% CI, 1.11-1.86, P = 0.006) than those born to treated mothers (n = 2846) after adjustment for confounding factors. A significantly higher risk of stillbirth (aOR = 3.68; 95% CI, 1.62-8.34, P = 0.002), preterm birth (aOR = 2.26; 95% CI, 1.71-3.00, P < 0.001), LBW (aOR = 2.23; 95% CI, 1.59-3.14, P < 0.001) and congenital syphilis (CS) (aOR = 3.63; 95% CI, 1.80-7.31, P < 0.001) was found in infants exposed to mothers treated inadequately (n = 1299) than those treated adequately (n = 1547). No pregnant women who initiated the treatment in the first trimester (n = 682) delivered a neonatal CS case. Compared with mothers who initiated treatment in the first trimester (n = 682), those initiated in the third trimester (n = 1234) suffered an increased risk of stillbirth (aOR = 4.48; 95% CI, 1.31-15.30, P = 0.017), preterm birth (aOR = 2.34; 95% CI, 1.61-3.40, P < 0.001) and LBW (aOR = 3.25; 95% CI, 1.97-5.37, P < 0.001). Conclusions: Maternal treatment, especially early and adequate treatment, plays a crucial role in mitigating adverse pregnancy outcomes among syphilis infected women.
Clinico-pathologic determinants of non-e-curative outcomes following en-bloc endoscopic submucosal dissection in patients with early gastric neoplasia
Authors: Embaye Kidane Siele , Zhang Chao , Ghebrehiwet Matiwos Araya , Wang Zhihao , Zhang Fengdi , Liu Liwei , Qin Shenghui , Qin Lingzhi , Wang Jun , Wang Xi
Published: September 2020

BackgroundEndoscopic submucosal dissection (ESD) is gaining enormous popularity in the treatment of early gastric cancers (EGCs) across many institutions in the world. However, appropriate selection of patients for endoscopic resection is crucial to sufficiently mitigate non-e-curative (NEC) resection. This study aims at identifying the various clinico-pathologic factors that independently predict the depth of submucosal invasion and NEC resection following ESD in patients with EGCs.MethodsMultiple logistic regression analysis was applied to investigate factors that independently predict the level of submucosal invasion and NEC resection in patients with early gastric neoplasia. Statistical Packages for the Social Sciences version 23 was used for analysis.ResultsA total of 162 EGCs underwent en-bloc ESD for which the rate of complete resection and non-e-curative outcomes were 95% and 22.2%, correspondingly. Multivariate analysis depicted that tumor location in the upper two third of stomach (odds ratio [OR] 5.46, confidence interval [CI] 95%, 1.65-18.12, p = 0.006), tumor size > 2 cm (OR 7.63, CI 95%, 2.29-25.42, p = 0.001), histologically undifferentiated tumor (OR 15.54, CI 95%, 1.65-146.22, p = 0.001), and tumors with 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc (OR 9.77, CI 95%, 1.23-77.65, p = 0.031) were all independent predictors of NEC resection for early gastric tumors. Additionally, location in the upper two third of stomach (OR 8.88, CI 95%, 2.90-27.17, p < 0.001), ulcerated lesions (OR 3.70, CI 95%, 1.15-11.90, p = 0.028), lesions with > 2 cm (OR 2.94, CI 95%, 1.08-8.02, p = 0.036) and those with poor differentiation (OR 6.51, CI 95%, 2.23-18.98, p = 0.001) were found to have significant association with submucosal invasion.ConclusionsTumors located in the upper two third of stomach having larger size (> 2 cm), poor histo-differentiation and a gross type of 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc are significantly associated with a risk of NEC after ESD procedure. Thus, early gastric tumors displaying these features need to be handled carefully during endoscopic resection. Our findings may provide some insights about the factors that determine non-curability in patients with EGC in relation to ESD procedure.
A Firefly Algorithm Based Hybrid Method for Structural Topology Optimization
Authors: Gebremedhen Hailu Shimels , Woldemichael Dereje Engida , Hashim Fakhruldin Mohd
Published: September 2020

In this paper, a firefly algorithm based hybrid algorithm through retaining global convergence of firefly algorithm and ability to generate connected topologies of optimality criteria (OC) method is proposed as an alternative method to solve stress-based topology optimization problems. The lower and upper limit of design variables (0 and 1) were used to find initial material distribution to initialize the firefly algorithm based section of the hybrid algorithm. Input parameters, the number of fireflies, and number function evaluations were determined before the implementation of the firefly algorithm to solve formulated problems. Since the direct application of the firefly algorithm cannot generate connected topologies, outputs from the firefly algorithm were used as an initial input material distribution for the OC method. The proposed method was validated using two-dimensional benchmark problems and the results were compared with results using the OC method. Weight percentage reduction, maximum stress-induced, optimal material distribution, and compliance were used to compare results. Results from the proposed method showed that the proposed method can generate connected topologies and generated topologies are free from the interference of end-users, which only dependence on boundary conditions or the design variables. From the results, the objective function (weight of the design domain) can be further reduced in the range of 5% to 15% compared to the OC method.
Implications of COVID-19 in high burden countries for HIV/TB: A systematic review of evidence
Authors: Tamuzi Jacques L , Birhanu Ayele T , Shumba Constance S , Adetokunboh Olatunji , Uwimana-Nico Jeannine , Haile Zelalem T , Inugu Joseph , Nyasulu Peter Suwirakwenda
Published: September 2020

Background: The triple burden of COVID-19, tuberculosis and human immunodeficiency virus is one of the major global health challenges of the 21st century. In high burden HIV/TB countries, the spread of COVID-19 among people living with HIV is a well-founded concern. A thorough understanding of HIV/TB and COVID-19 pandemics is important as the three diseases interact. This may clarify HIV/TB/COVID-19 as a newly related field. However, several gaps remain in the knowledge of the burden of COVID-19 on patients with TB and HIV. This study was conducted to review different studies on SARS-CoV, MERS-CoV or COVID-19 associated with HIV/TB co-infection or only TB, to understand the interactions between HIV, TB and COVID-19 and its implications on the burden of the COVID-19 among HIV/TB co-infected or TB patients, screening algorithm and clinical management.Methods: We conducted an electronic search of potentially eligible studies published in English in the Cochrane Controlled Register of Trials, PubMed, Medrxiv, Google scholar and Clinical Trials Registry databases. We included case studies, case series and observational studies published between January, 2002 and July, 2020 in which SARS-CoV, MERS-CoV and COVID-19 co-infected to HIV/TB or TB in adults. We screened titles, abstracts and full articles for eligibility. Descriptive and meta-analysis were done and results have been presented in graphs and tables.Results: After removing 95 duplicates, 58 out of 437 articles were assessed for eligibility, of which 14 studies were included for descriptive analysis and seven studies were included in the meta-analysis. Compared to the descriptive analysis, the meta-analysis showed strong evidence that current TB exposure was high-risk COVID-19 group (OR 1.67, 95% CI 1.06-2.65, P= 0.03). The pooled of COVID-19/TB severity rate increased from OR 4.50 (95% CI 1.12-18.10, P=0.03), the recovery rate was high among COVID-19 compared to COVID-19/TB irrespective of HIV status (OR 2.23, 95% CI 1.83-2.74, P < 0.001) and the mortality was reduced among non-TB group (P<0.001).Conclusion: In summary, TB was a risk factor for COVID-19 both in terms of severity and mortality irrespective of HIV status. Structured diagnostic algorithms and clinical management are suggested to improve COVID-19/HIV/TB or COVID-19/TB co-infections outcomes.
Serum Neutrophil Gelatinase-associated Lipocalin at 3 Hours after Return of Spontaneous Circulation in Patients with Cardiac Arrest and Therapeutic Hypothermia: Early Predictor of Acute Kidney Injury
Authors: Choi Yoon Hee , Lee Dong Hoon , Lee Jae Hee
Published: September 2020

Background: Serum neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary from immediately after ROSC to several days later. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 hours after ROSC (3h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge.Methods: This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. The serum NGAL level was measured both immediately and 3 hours after ROSC. Univariate and multivariate analyses were performed to identify the associations between AKI, poor neurologic outcome, and NGAL.Results: Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009–1.035; p = 0.001). The area under the receiver operating characteristic curve of 3h-NGAL for AKI was 0.910 (95% CI 0.830–0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis (ROSC-NGAL; OR 1.017; 95% CI 0.998–1.036; p = 0.084, 3h-NGAL; OR 0.997; 95% CI 0.992–1.001; p = 0.113)Conclusions: The serum NGAL concentration measured 3 hours after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research.
Contribution of root respiration to total soil respiration during non-growing season in mine reclaimed soil with different covering soil thicknesses
Authors: Chen Min , Chen Xiaoyang , Hu Zhiyong , Fan Tingyu , Zhang Shiwen , Liu Ying
Published: September 2020

An accurate assessment of root respiration in mine reclaimed soil is important for effectively evaluating mining area ecosystem. This study investigated dynamic changes in root respiration and contribution of root respiration to total soil respiration (Rr/Rt ratio) during the non-growing season in mine reclaimed soil with different covering soil thicknesses. According to covering soil thicknesses, the study area was divided into four sites: 10-25 cm (site A), 25-45 cm (site B), 45-55 cm (site C) and 55-65 cm (site D). From November 2017 to April 2018 (except February in 2018), the soil respiration, root respiration, temperature at 5 cm, water content and root biomass were measured. The results showed that soil temperature and root respiration exhibited similar diurnal and monthly variations. The root respiration was strongly influenced by soil temperature during the non-growing season, which showed an exponential and positive relationship with soil temperature (P<0.001). The root respiration varied with the covering soil thickness and was the greatest with the covering soil thickness at 25–45 cm. The Rr/Rt ratio also exhibited monthly variations. During the non-growing season, the mean value of the Rr/Rt ratio was 51.15% in mine reclaimed soil. The study indicated that root respiration was the primary source of soil respiration and important to estimate the potential emission of soil CO2 at regional scale in mine reclaimed soil.
MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
Authors: Alexander Cyrus , Guru Ankeeta , Pradhan Pinkilata , Mallick Sunanda , Mahanandia Nimai Charan , Subudhi Bharat Bhushan , Beuria Tushar Kant
Published: September 2020

Background: Persistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance of various infections increasing the treatment time and costs. Additionally, some studies also indicate that persistence can also pave way for the emergence of resistant strains. In a laboratory setting this persistent phenotype is enriched in nutritionally deprived environments. Consequently, in a batch culture the late stationary phase is enriched with persistent bacteria. The mechanism of persister cell formation and its regulation is not well understood. Toxin-antitoxins (TA) systems have been implicated to be responsible for bacterial persistence and rifampicin is used to treat highly persistent bacterial strains. The current study tries to explore a possible interaction between rifampicin and the MazEF TA system that furthers the former’s success rate in treating persistent bacteria. Results: In the current study we found that the population of bacteria in the death phase of a batch culture consists of metabolically inactive live cells resembling persisters, which showed higher membrane depolarization as compared to the log phase bacteria. We also observed an increase in the expression of the MazEF TA modules in this phase. Since rifampicin is used to kill the persisters, we assessed the interaction of rifampicin with MazEF complex. We showed that rifampicin moderately interacts with MazEF complex with 1:1 stoichiometry.Conclusion: Our study suggests that the interaction of rifampicin with MazEF complex might play an important role in inhibition of persisters.
Feasibility of remote digital monitoring using wireless Bluetooth monitors, the Smart AngelTM app and an original web platform for patients following outpatient surgery: A prospective observational pilot study.
Authors: Chevallier Thierry , Buzancais Gautier , Occean Bob-valery , Rataboul Pierre , Boisson Christophe , simon natacha , Lannelongue Ariane , Chaniaud Noemie , Gricourt Yann , Lefrant Jean-Yves , cuvillon philippe
Published: September 2020

Background Remote monitoring of mean arterial blood pressure (MAP), heart rate (HR) or oxygen saturation (SpO2) remains a challenge in outpatient surgery. This study evaluates a new digital technology (Smart AngelTM) for remotely monitoring hemodynamic data in real time: data transmitted from the patient's home to a central server, using a dedicated web-based software package.Methods Adults scheduled for elective outpatient surgery were prospectively enrolled. In the first 5 postoperative days, patients completed a self-report questionnaire (pain, comfort, nausea, vomiting) and recorded SpO2, HR and MAP via two wireless Bluetooth monitors connected to a 4G tablet to transmit the data to a website, in real time, using Smart AngelTM software. Before transmission to the website, these data were also self-reported by the patient on a paper form. The primary outcome was the proportion of variables (self-monitored physiological data + questionnaire scores) correctly transmitted to the hospital via the system compared with the paper version. On Day 5, a system usability scale survey (SUS score 1-100) was also attributed.Results From May 2018 to September 2018, data were available for 29 out of 30 patients enrolled (1 patient was not discharged from hospital after surgery). The remote monitoring technology recorded 2038 data items (62%) compared with 2656 (82%) items recorded on the paper form (p=0.001). The most common errors with the remote technology were software malfunctioning when starting the MAP monitor and malfunctioning between the tablet and the Bluetooth monitor. No serious adverse events were noted. The SUS score for the system was 85 (68-93) for 26 patients.Conclusion This work evaluates the ability of a pilot system for monitoring remote physiological data using digital technology after ambulatory surgery and highlights the digital limitations of this technology. Technological improvements are required to reduce malfunctioning (4G access, transmission between apps).Trial registration: ClinicalTrials.gov (NCT03464721) (March 8, 2018)
Ethnobotanical knowledge on non-conventional food and medicinal plants in Rio Cajari Extractivist Reserve, Amazon, Brazil
Authors: Filho Galdino Xavier de Paula , Ribeiro Adivair Freitas , Moraes Alcidete Flexa , Penha Willis Freitas , Borges Wardsson Lustrino , Santos Ricardo Henrique Silva
Published: September 2020

Background: Information on the knowledge, management and ways of using food and medicinal plants by traditional populations, family farmers and Brazilian native population in the Amazon is essential to guarantee the sovereignty of these groups. The objective of this study was to evaluate the diversity, knowledge and ways of using non-conventional food and medicinal plants in traditional communities in a protected area in the Brazilian Amazon. Methods: This study was conducted using semi-structured interviews applied to local respondents. Fifty-six residents were interviewed in 26 communities. The Indices of Use Value (UVI) and relative frequency of species citation (Fr) were evaluated; also, their diversity and equitability using the Shannon- Wiener (H’) Pielou (J’) indices, respectively. The species were listed according to their family, scientific name, popular names, categories of use, propagation environment, growth habit, medicinal indications, domestication status, production cycle, and herbarium registration. Results: A total of 269 species of both non-conventional food and medicinal plants were identified, distributed in 84 botanical families, 198 genera, in addition to 13 unidentified species. The Arecaceae and Lamiaceae families had the highest species richness (11 and 7, respectively). Eryngium foetidum L. (Apiaceae) and Ipomoea batatas L. (Convolvulaceae) presented the highest relative citation frequencies (19.7 and 19.3, respectively) and the highest index of use value of the species (0.94 and 0.92, respectively). The Shannon-Wiener (H’) and Pielou (J’) diversity indices were considered high (5.02 and 0.9, respectively). Conclusions: It was observed that the studied species are consumed daily by the population of this protected area. In the environment in which these families are found, of geographical isolation and distance from urban centers, these species become the only food and medicinal resources, therefore, being fundamental to the sovereignty of these families.
Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N
Authors: Bono Keiko , Miyauchi-Hara Chikako , Sumi Shunsuke , Oka Hisayoshi , Iguchi Yasuyuki , Okano Hirotaka James
Published: September 2020

Mutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons from PD patients with the VPS35 D620N mutation and addressed relevant disease mechanisms. In the disease group, dopaminergic (DA) neurons underwent extensive apoptotic cell death. The movement of Rab5a- or Rab7a-positive endosomes was slower, and the endosome fission and fusion frequencies were lower in the PD group than in the healthy control group. Interestingly, vesicles positive for cation-independent mannose 6-phosphate receptor transported by retromers were abnormally localized in glial cells derived from patient iPSCs. Furthermore, we found a-synuclein accumulation in TH positive DA neurons. Our results demonstrate the induction of cell death, endosomal dysfunction and a-synuclein accumulation in neural cells of the PD group. PARK17 patient-derived iPSCs provide an excellent experimental tool for understanding the pathophysiology underlying PD.
Stagewise resolution of temperature-dependent embryonic and postembryonic development in the cowpea seed beetle Callosobruchus maculatus (F.)
Authors: Kutcherov Dmitry
Published: September 2020

Background: The thermal plasticity of life-history traits receives wide attention in the recent biological literature. Of all the temperature-dependent traits studied, developmental rates of ectotherms are especially often addressed, and yet surprisingly little is known about embryonic responses to temperature, including changes in the thermal thresholds and thermal sensitivity during early development. Even postembryonic development of many cryptically living species is understood superficially at best. Results: This study is the first to estimate the exact durations of developmental stages in the cowpea seed beetle C. maculatus from oviposition to adult emergence at five permissive constant temperatures from 20 to 32°C. Early embryonic development was tracked and documented by means of destructive sampling and subsequent confocal imaging of fluorescently stained specimens. Late embryonic and early larval development was studied with the use of destructive sampling and light microscopy. Well-resolved temporal series based on thousands of embryos allowed precise timing of the following developmental events: formation of the blastoderm; formation, elongation, and retraction of the germ band; dorsal closure; the onset and completion of sclerotization of the cuticle; hatching, and penetration of the first-instar larva into the cowpea seed. Pupation and adult eclosion were observed directly through an incision in the seed coat. The thermal phenotype of C. maculatus was found to vary in the course of ontogeny and different stages scaled disproportionately with temperature, but pitfalls and caveats associated with analyses of relative durations of individual stages are also briefly discussed. Conclusion: Disproportionate changes in developmental durations with temperature may have important implications when study design requires a high degree of synchronization among experimental embryos or when the occurrence of particular stages in the field is of interest, as well as in any other cases when development times need to be estimated with precision. This work provides one of the first examples of integration of embryological techniques with ecophysiological concepts and will hopefully motivate similar projects in the future. While experiments with Drosophila continue to be the main source of information on animal development, knowledge on other model species is instrumental to building a broader picture of developmental phenomena.
Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation is associated with partial recessive red phenotypes in dog
Authors: Anderson Heidi , Honkanen Leena , Ruotanen Päivi , Mathlin Julia , Donner Jonas
Published: September 2020

Background: The Melanocortin 1 Receptor (MC1R) plays a central role in regulation of coat color determination in dogs and is commonly referred to as the “E (extension) Locus”. Allelic variation of the MC1R gene is associated with coat color phenotypes EM (melanistic mask), EG (grizzle/domino) and e1-3 (recessive red) in dogs. In addition, a previous study of archeological dog specimens over 10,000 years of age identified a variant p.R301C in the MC1R gene that may have influenced coat color of early dogs.Results: Commercial genotyping of 11,750 dog samples showed the R301C variant of the MC1R gene was present in 35 breeds or breed varieties, at an allele frequency of 1.5% in the tested population. We detected no linkage disequilibrium between R301C and other tested alleles of the E locus. Based on current convention we propose that R301C should be considered a novel allele of the E locus, which we have termed eA for “e ancient red”. Phenotype analysis of owner-provided dog pictures reveals that the eA allele has an impact on coat color and is recessive to wild type E and dominant to the e alleles. In dominant black (KB/*) dogs it can prevent the expression of the K locus, and the expressed coat color is solely determined by the A locus. In the absence of dominant black, eA/eA and eA/e genotypes result in the coat color patterns referred to in their respective breed communities as domino in Alaskan Malamute and other Spitz breeds, grizzle in Chihuahua, and pied in Beagle.Conclusions: This study demonstrates a large genotype screening effort to identify the frequency and distribution of the MC1R R301C variant, one of the earliest mutations captured by canine domestication, and citizen science empowered characterization of its impact on coat color.
Combination of SB431542, Chir9901, and Bpv as a novel supplement in the culture of umbilical cord blood hematopoietic stem cells
Authors: Zarrabi Morteza , Afzal Elaheh , Asghari Mohammad Hassan , Ebrahimi Marzieh
Published: September 2020

Background: Small molecule compounds have been well recognized for their promising power in generation, expansion and maintenance of embryonic or adult stem cells. The aim of this study was to identify a novel combination of small molecules in order to optimize the ex vivo expansion of umbilical cord blood derived-CD34+ cells. Methods: Considering the most important signaling pathways involved in the self-renewal of hematopoietic stem cells, CB-CD34+ cells were expanded with cytokines in the presence of seven small molecules including SB, PD, Chir, Bpv, Pur, Pμ and NAM. Eliminativism approach was used to find the best combination of selected small molecules for effective ex vivo expansion of CD34+ cell. In each step, proliferation, self-renewal, and clonogenic potential of the expanded cells as well as expression of some hematopoietic stem cell related genes were studied. Finally, the engraftment potential of expanded cells was also examined by the mouse intra-uterine transplantation model. Results: Our data shows that simultaneous use of SB431542 (TGF-β inhibitor), Chir9901 (GSK3 inhibitor) and Bpv (PTEN inhibitor), resulted in a 50-fold increase in the number of CD34+CD38- cells. This was further reflected in approximately 3 times increase in clonogenic potential of the small molecule cocktail-expanded cells. These cells, also, showed a 1.5-fold higher engraftment potential in the peripheral blood of NMRI model of in utero transplantation. These results are in total conformity with up-regulation of HOXB4, GATA2 and CD34 marker gene as well as CXCR4 homing gene. Conclusion: Taken together, our findings introduce a novel combination of small molecules to improve the yield of existing protocols used in the expansion of hematopoietic stem cells.
Genome-wide identification and functional characterization of Camelina sativa WRKY gene family in response to abiotic stress
Authors: Song Yanan , Cui Hongli , Shi Ying , Xue Jinai , Ji Chunli , Zhang Chunhui , Yuan Lixia , Li Runzhi
Published: September 2020

Background: WRKY transcription factors are a superfamily of regulators involved in diverse biological processes and stress responses in plants. However, knowledge is limited for WRKY family in camelina (Camelina sativa), an important Brassicaceae oil crop with strong tolerance against various stresses. Here, genome-wide characterization of WRKY proteins is performed to examine their gene-structures, phylogenetics, expressions, conserved motif organizations, and functional annotation to identify candidate WRKYs mediating regulation of stress resistance in camelina. Results: Total of 242 CsWRKY proteins encoded by 224 gene loci distributed uneven on chromosomes were identified, and classified into three groups via phylogenetic analysis according to their WRKY domains and zinc finger motifs. 15 CsWRKY gene loci generated 33 spliced variants. Orthologous WRKY gene pairs were identified, with 173 pairs in C. sativa and Arabidopsis genomes as well as 282 pairs for C. sativa and B. napus, respectively. 137 segmental duplication events were observed but no tandem duplication in camelina genome. Ten major conserved motifs were examined, with WRKYGQK as the most conserved and several variants existed in many CsWRKYs. Expression analysis revealed that half more CsWRKY genes were expressed constitutively, and a set of them had a tissue-specific expression. Notably, 11 CsWRKY genes exhibited significantly expression changes in plant seedlings under cold, salt, and drought stress, respectively, having preferentially inducible expression pattern in response to the stress. Conclusions: The present described a detail analysis of CsWRKY gen family and their expression profiled in twelve tissues and under several stress conditions. Segmental duplication is the major force for large expansion of this gene family, and a strong purifying pressure happened for CsWRKY proteins evolutionally. CsWRKY proteins play important roles for plant development, with differential functions in different tissues. Exceptionally, eleven CsWRKYs, particularly five alternative spliced isoforms were found to be the key players possibly in mediating plant response to various stresses. Overall, our results provide a foundation for understanding roles of CsWRKYs and the precise mechanism through which CsWRKYs regulate high stress resistance to stress as well as development of stress tolerance cultivars for Cruciferae crops.
Pregnancy vs. Paycheck: A qualitative study of patient’s experience with employment during pregnancy at high risk for preterm birth
Authors: Wheeler Sarahn M. , Massengale Kelley E. C. , Adewumi Konyin , Fitzgerald Thelma A. , Dombeck Carrie B. , Swezey Teresa , Swamy Geeta K. , Corneli Amy
Published: September 2020

Background: Pregnant women with a history of preterm birth are at risk for recurrence, often requiring frequent prenatal visits for close monitoring and/or preventive therapies. Employment demands can limit uptake and adherence to recommended monitoring and preterm birth prevention therapies. Method: We conducted a qualitative descriptive study using in-depth interviews (IDIs) of pregnant women with a history of preterm birth. IDIs were conducted by trained qualitative interviewers following a semi-structured interview guide focused on uncovering barriers and facilitators to initiation of prenatal care, including relevant employment experiences, and soliciting potential interventions to improve prompt prenatal care initiation. The IDIs were analyzed via applied thematic analysis. Results: We described the interview findings that address women’s employment experiences. The current analysis includes 27 women who are majority self-described as non-Hispanic Black (74%) and publically insured (70%). Participants were employed in a range of professions; food services, childcare and retail were the most common occupations. Participants described multiple ways that being pregnant impacted their earning potential, ranging from voluntary work-hour reduction, involuntary duty hour reductions by employers, truncated promotions, and termination of employment. Participants also shared varying experiences with workplace accommodations to their work environment and job duties based on their pregnancy. Some of these accommodations were initiated by a collaborative employee/employer discussion, others were initiated by the employer’s perception of safe working conditions in pregnancy, and some accommodations were based on medical recommendations. Participants described supportive and unsupportive employer reactions to requests for accommodations. Conclusions: Our findings provide novel insights into women’s experiences balancing a pregnancy at increased risk for preterm birth with employment obligations. While many women reported positive experiences, the most striking insights came from women who described negative situations that ranged from challenging to potentially unlawful. Many of the findings suggest profound misunderstandings likely exist at the patient, employer and clinical provider level about the laws surrounding employment in pregnancy, safe employment responsibilities during pregnancy, and the range of creative accommodations that often allow for continued workplace productivity even during high risk pregnancy.
Global Optimization Of A Numerical Two-Layer Model Using Observed Data: A Case Study Of The 2018 Sunda Strait Tsunami
Authors: Pakoksung Kwanchai , Suppasri Anawat , Abdul Muhari , Syamsidik Syamsidik , Imamura Fumihiko
Published: September 2020

Following the eruption of Mount Anak Krakatau, a considerable landslide occurred on the southwestern part of the volcano and, upon entering the sea, generated a large tsunami within the Sunda Strait, Indonesia, on 22 December 2018. This tsunami traveled ~5 km across the strait basin and inundated the shorelines of Sumatra and Java with a vertical runup reaching 13 m. Following the event, observed field data, GPS measurements of the inundation, and multibeam echo soundings of the bathymetry within the strait were collected and publicly provided. Using this dataset, numerical modeling of the tsunami was conducted using the two-layer (soil and water) TUNAMI-N2 model based on a combination of landslide sources and bathymetry data. The two-layer model was implemented to nest the grid system using a finest grid size of 20 m. To constrain the unknown landslide parameters, the differential evolution (DE) global optimization algorithm was applied, which resulted in a parameter set that minimized the deviation from the measured bathymetry after the event. The DE global optimization procedure was effective at determining the landslide parameters for the model with the minimum deviation from the measured seafloor. The lowest deviation from the measured bathymetry was obtained for the best-fitting parameters: a maximum landslide thickness of 301.2 m and a landslide time of 10.8 minutes. The landslide volume of 0.182 km3 estimated by the best-fitting parameters shows that the tsunami flow depth could have reached 3-10 m along the shore with a K value of 0.89, although the simulated flow depths were underestimated in comparison with the observation data. According to the waveforms, the general wave pattern was well reproduced at tide gauges during the event. A large number of objective function evaluations were necessary to locate the minimum with the DE procedure to fix the grid cell size to 20 m; this limited the accuracy of the obtained parameter values for the two-layer model. Moreover, considering the generalizations in the modeling of landslide movements, the impact landslide time and thickness must be carefully calculated to obtain a suitable accuracy.