bluuebunny/crossref_metadata_2025 huggingface dataset:
Rabies virus phosphoprotein P5 binding to BECN1 regulates self-replication by BECN1-mediated autophagy signaling pathway
Authors: Liu Juan , Liao Min , Yan Yan , Yang Hui , Wang Hailong , Zhou Jiyong
Published: July 2020

Background: Rabies virus (RABV) is reported to encode five phosphoproteins (P), which are involved in viral genomic replication, axonal transport, oxidative stress, interferon antagonism, and autophagy induction. However, the functions of the different P proteins are poorly understood. Methods: Immunofluorescence staining and western blot were performed to detect the autophagy activity, the form of ring-like structure, and the colocalization of BECN1 and P. Co-immunoprecipitation was performed to detect the interaction between P and BECN1. QRT-PCR and TCID50 assay were performed to detect the replication level of RABV. Small interfering RNA was used to detect the autophagy signaling pathway. Results: We found that P5 attaches to N-terminal residues 1–139 of BECN1 (beclin1) on the BECN1 ring-like structure through amino acid residues 173–222 of P5. Subsequently, we found that P5-induced autophagosomes did not fuse with lysosomes. Becn1 silencing did not recover P5 overexpression-induced promotion of RABV replication. Mechanistically, RABV protein PΔN82 (P5) induced incomplete autophagy via the BECN1-mediated signaling pathway.Conclusions: Our data indicate that P5 binding to the BECN1 ring benefits RABV replication by inducing BECN1 signaling pathway-dependent incomplete autophagy, which provides a potential target for antiviral drugs against RABV.
The Pearl River Declaration: a timely call for enhancing health security through fostering a regional One Health collaboration in the Asia-Pacific
Authors: Alam Noore , Chu Cordia , Li Qianlin , Crook Allison , Whittaker Maxine , Aditama Tjandra , Schak Elena , Budiman Dicky , Barber Bonnie , Lu Jiahai
Published: July 2020

The Second International Symposium on One Health Research (ISOHR) was held in Guangzhou city, China on 23–24 November 2019. A transdisciplinary collaborative approach, One Health (OH), was the central theme of the symposium which brought together more than 260 experts, scholars and emerging researchers from human health, veterinary health, food safety, environmental health and related disciplines and sectors. More than 50 organizations including World Health Organization, Centers for Disease Control (USA), and Queensland Government (Australia) participated in the symposium. Scholars, experts and emerging researchers, policy-makers and practitioners in their respective fields delivered over 50 presentations at the symposium, highlighting the collective vulnerability to some of the emerging health challenges the region was combating. These included emerging infectious diseases, antimicrobial resistance, climate change, food safety and the growing burden of non-communicable diseases. The Pearl River Declaration , emanated from the symposium, called for establishing a One Health Cooperation Network in the Southeast Asia–Pacific region with a vision to strengthen regional health security through sharing each other’s knowledge and experience, and making investments in workforce development, scientific innovations such as vaccine research and development, sharing epidemic intelligence, risk identification, risk communication and appropriate response measures against emerging health threats.
Gender Differences In Quality Of Life In Adults With Long-Standing Type 1 Diabetes Mellitus
Authors: Castellano-Guerrero Ana , Guerrero Raquel , Ruiz-Aranda Desiree , Perea Sofia , Pumar Alfonso , Relimpio Federico , Mangas Miguel Angel , Losada Fernando , Martínez-Brocca Maria Asuncion
Published: July 2020

Background: To assess gender differences in Quality of life (QoL) and in sociodemographic, clinical and psychological factors associated with impaired QoL in adults with long-standing type 1 diabetes mellitus (DM1). Methods: Cross-sectional evaluation in a random cohort of DM1 adult patients from a tertiary care hospital. QoL was evaluated using translated and validated self-administered Diabetes QoL questionnaire (Es-DQoL), and results transformed into a 0-100 scale. Psychological assessment included a planned psychological interview and self-reported questionnaires (Beck Depression Inventory II, State-Trait Anxiety Inventory Form Y, Fear of hypoglycaemia Scale, Medical Outcomes Study Social Support Survey). Results: A total of 312 patients (51.6% male; 38.2 ± 12.7 years; HbA1c 7.5 ± 1.1% (58.5 ± 14.2 mmol/mol); 20.4 ± 12.0 years of DM1) were included in the analysis. Male and female subgroups showed similar sociodemographic and diabetes-related features and comparable social support. Among female patients, higher frequency of depression [31.7% (IC95% 26.2-40.8) vs. 14.9% (IC95% 10.1-20.8), p<0.05] and anxiety [23.2% (IC95% 19.3-33.14) vs. 13.0% (IC95% 8.1-18.4), p<0.05] and severity of depressive and anxious symptoms were also found. Compared to male patients, female patients showed lower QoL [75 (IC95% 73.6-77.5) vs. 80 (IC95% 75.7-83.1), p<0.05] and scored significantly worse in subscale Diabetes-related worries [69 (IC95% 50-81) vs. 75 (IC95% 72.9-79.0), p<0.05]. Fear of hypoglycemia and severity of depressive and anxious symptoms and were factors independently associated to lower QoL in men and women while high frequency of glycemic excursions was a female-specific predictive one. Conclusions: Adult women with long-standing DM1 showed lower QoL probably related to higher frequency and severity of psychopathological syndromes. Depressive and anxious symptoms and, among women, exposure to glycemic excursions were identified as modifiable, QoL-related variables. Educational, technological and psychological interventions are needed in order to improve QoL in DM1 patients.
Using volunteered geographic information to assess mobility in the COVID-19 pandemic context: cross-city time series analysis of 41 cities in 22 countries from March 2nd to 26th 2020
Authors: Vanoni Matia , McKee Martin , Bonell Chris , Semenza Jan , Stuckler David
Published: July 2020

Objectives: Restricting mobility is a central aim for lowering contact rates and preventing COVID-19 transmission. Yet the impact on mobility of different non-pharmaceutical countermeasures in the earlier stages of the pandemic is not well-understood.Design: Trends were evaluated using Citymapper’s mobility index covering 2nd to 26th March 2020, expressed as percentages of typical usage periods from 0% as the lowest and 100% as normal. China and India were not covered. Multivariate fixed effects models were used to estimate the association of policies restricting movement on mobility before and after their introduction. Policy restrictions were assessed using the Oxford COVID-19 Government Response Stringency Index as well as measures coding the timing and degree of school and workplace closures, transport restrictions, and cancellation of mass gatherings.Setting: 41 cities worldwideMain outcome measures: Citymapper’s mobility indexResults: Mobility declined in all major cities throughout March. Larger declines were seen in European than Asian cities. The COVID-19 Government Response Stringency Index was strongly associated with declines in mobility (r = -0.75, p<0.001). After adjusting for time-trends, we observed that implementing non-pharmaceutical countermeasures was associated with a decline of mobility of 10.0% for school closures (95% CI: 4.36% to 15.7%), 15.0% for workplace closures (95% CI: 10.2% to 19.8%), 7.09% for cancelling public events (95% CI: 1.98% to 12.2%), 18.0% for closing public transport (95% CI: 6.74% to 29.2%), 13.3% for restricting internal movements (95% CI: 8.85% to 17.8%) and 5.30% for international travel controls (95% CI: 1.69 to 8.90). In contrast, as expected, there was no association between population mobility changes and fiscal or monetary measures or emergency healthcare investment.Conclusions: Understanding the effect of public policy on mobility in the early stages is crucial to slowing and reducing COVID-19 transmission. By using Citymapper’s mobility index, this work provides the first evidence about trends in mobility and the impacts of different policy interventions, suggesting that closure of public transport, workplaces and schools are particularly impactful.Summary boxWhat is already known on this topic?Governments across the global are experimenting with a range of policy interventions to restrict movement in populations. Yet their impact is not well understood. There is an urgent need to understand how alternative policy approaches to restricting movement can impact on population mobility trends. What this study addsOur study finds that policy restrictions markedly reduced population-wide mobility. Closing public transport, workplaces and schools have among the largest associations with mobility declines.
Surgery combined with antibiotics for the treatment of endogenous endophthalmitis caused by live abscess
Authors: Wang Yue , Wang Xue , Di Yu
Published: July 2020

Backgrounds: Endogenous endophthalmitis is a serious disease caused by intraocular infection that can rapidly progress to cause blindness. This study evaluated the clinical features, surgical and antibiotics treatment strategies, and treatment outcomes in patients with endophthalmitis caused by liver abscess.Methods: Between April 2014 and April 2019, the clinical data of 16 patients (19 eyes) with endophthalmitis associated with liver abscess who underwent surgery at Shengjing Hospital were retrospectively analyzed. Furthermore, we evaluated the final visual outcomes in the patients to determine the efficacy of surgery.Results: Fifteen patients (18 eyes) underwent intravitreal injection followed by vitrectomy after admission. One patient (1 eye) only underwent intravitreal injection. Of the 16 patients, 3 patients (3 eyes) had recurrent intraocular inflammation and eventually underwent evisceration. Systemic antibiotics were administered for all patients based on the results of vitreous humor culture, blood culture, and antibiotic susceptibility tests. Outpatient follow-ups were performed until the patients were stable (6 months). Of the 19 eyes, 1 eye (5%) had visual acuity restored to 20/200, 6 eyes (31%) had visual acuity restored to counting fingers (CF), 2 eyes (11%) had visual acuity restored to hand motion (HM), 4 eyes (22%) showed only light perception (LP), and the remaining 6 eyes (31%) showed no light perception (NLP). Drug susceptibility tests suggested that the carbapenems exhibited significant effects in the inflammatory reaction.Conclusion: Endogenous endophthalmitis caused by liver abscess is a very serious condition, and the final visual outcome is poor. Timely surgical intervention combined with antibiotic treatment is essential, and the primary disease must be treated to control disease progression at the earliest.
The impact of scrubber discharge on the water quality in estuaries and ports
Authors: Teuchies Johannes , Cox Tom J.S. , Itterbeeck Katrien Van , Me Filip J.R. , Blust Ronny
Published: July 2020

Background: The International Maritime Organization (IMO) has set limits on sulphur content in fuels for marine transport. However, vessels continue to use these residual high sulphur fuels in combination with exhaust gas cleaning systems (EGCS or scrubbers). Next to high sulphur, combustion of these fuels also results in higher emissions of contaminants including metals and PAHs. In scrubbers, exhaust gases are sprayed with water in order to remove SOx, resulting in acidic washwater with elevated contaminant concentrations discharged in the aquatic ecosystem. The number of vessels with scrubbers is increasing rapidly, but knowledge on washwater quality and impact are limited. Results: The scrubber washwater is found to be acidic with elevated concentrations of e.g. zinc, vanadium, copper, nickel, phenanthrene, naphthalene, fluorene and fluoranthene. Model calculations on the effects of scrubber discharge under scenario HIGH (20% of vessels, 90th percentile concentrations) on the water quality in harbor docks showed a decrease in pH of 0.015 units and an increase in surface water concentrations for e.g. naphthalene (189% increase) and vanadium (46% increase). Conclusions: The IMO established sulphur regulations to mitigate the impact of high sulphur emissions of the maritime sector. However, the use of open loop scrubbers as an abatement technology will not reduce their contribution to ocean acidification. In addition, different types of scrubbers discharge washwater that is acute toxic for aquatic organisms. However, washwater is diluted and the compounds for which a large increase in surface water concentrations was calculated in the Antwerp (Belgium) harbour docks (Naphthalene > Phenanthrene > Fluorene > Acenaphthene > Vanadium) were not the compounds that already exceed their respective Water Quality Standards (WQS). Nevertheless, the WQS of several ‘priority hazardous substances’ (Water Framework Directive) are already exceeded in the docks and the Scheldt estuary. Since these hazardous substances are also identified in the washwater, scrubber washwater discharge should be discouraged in coastal waters and estuaries with large ecological value.
Physicians’ attitudes in relation to End-of-life Decisions in Neonatal Intensive Care Units: a national multicenter survey
Authors: Chatziioannidis Ilias , Iliodromiti Zoi , Boutsikou Theodora , Pouliakis Abraham , Giougi Evangelia , Sokou Rozeta , Vidalis Takis , Xanthos Theodoros , Cuttini Marina , Iacovidou Nicoletta
Published: July 2020

Background: End-of-life decisions for neonates with adverse prognosis are controversial and raise ethical and legal issues. In Greece, data on physicians’ profiles, motivation, values and attitudes underlying such decisions and the correlation with their background are scarce. The aim was to investigate neonatologists' attitudes in neonatal intensive care units and correlate them with self-reported practices of end-of-life decisions and with their background data. Methods: A structured questionnaire was distributed to all 28 Neonatal Intensive Care Units in Greece. One hundred and sixty two out of 260 eligible physicians answered anonymously the questionnaire (response rate 66%). Demographic and professional characteristics, self-reported practices and opinions were included in the questionnaire, along with a questionnaire of 12 items measuring physicians’ attitude and views ranging from value of life to quality of life approach (scale 1 to 5). Results: Continuation of treatment in neonates with adverse prognosis without adding further therapeutic interventions was the most commonly reported EoL practice, when compared to withdrawal of mechanical ventilation. Physicians with a high attitude score (indicative of value of quality-of-life) were more likely to limit, while those with a low score (indicative of value of sanctity-of-life) were more likely for continuation of intensive care. Physicians’ educational level (p:0.097), involvement in research (p:0.093), religion (p:0.024) and position on the existing legal framework (p<0.001) were factors that affected the attitude score. Conclusions: Physicians presented with varying end-of-life practices. Limiting interventions in neonates with poor prognosis was strongly related to their attitudes. The most important predictors for physicians' attitudes were religiousness and belief for Greek legal system reform.
Two rare cases of acute myeloid leukemia with t(8;16)(p11.2;p13.3) and 1q duplication: case presentation and literature review
Authors: Liu Meng , Ren Yuan , Wang Xianfu , Lu Xianglan , Li Ming , Kim Young Mi , Li Shibo , Zhang Lijun
Published: July 2020

Background: Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. The identification and understanding of chromosomal abnormalities are important for the diagnosis and management of AML patients. Compared to recurrent chromosomal translocations in AML, t(8;16)(p11.2;p13.3) can be found in any age group, but is very rare and typically associated with poor prognosis. Methods: Conventional cytogenetic studies were performed among 1,824 AML patients from our oncology database in the last 20 years. Fluorescence in situ hybridization (FISH) was carried out to demonstrate the translocation fusion. Array comparative genome hybridization (aCGH) was carried out to further characterize the duplication of chromosomes.Results: We identified three AML patients with t(8;16)(p11.2;p13.3) by chromosome analysis. Two of the three patients with additional 1q duplication were detected by FISH and aCGH. aCGH characterized a 46.7 Mb and 49.9 Mb gain of chromosome 1 at bands q32.1q44 in these two patients, respectively. One patient achieved a complete remission (CR) but relapsed three months later. The other patient never experienced a CR and died two years after diagnosis. Conclusion: 1q duplication were detected in two of three AML patients with t(8;16)(p11.2;p13.3), suggesting that 1q duplication can be a recurrent event in AML patients with t(8;16). In concert with the findings of previous studies of similar patients, our work suggests that 1q duplication may also be an unfavorable prognostic factor of the disease.
Characterization of a Monanema nematode in Ixodes scapularis
Authors: Tokarz Rafal , Tagliafierro Teresa , Lipkin W. Ian , Marques Adriana R
Published: July 2020

Background: Metagenomic studies have revealed the presence of a filarial nematode in Ixodes scapularis. The phylogeny of this agent, and its potential for human infection, are unknown.Methods: We used existing metagenomic data from I. scapularis to determine the phylogeny of this tick-associated nematode and employed quantitative PCR to determine if the presence of this agent had an effect on the burden of Borrelia burgdorferi. We also developed a Luciferase Immunoprecipitation System assay using the Av33 antigen as a target to investigate the presence of antibodies against this nematode in 128 serum specimens from patients with Lyme disease and babesiosis. To demonstrate assay utility, we used 15 sera from patients with onchocerciasis as controls.Results: We show that this agent is a new species in the genus Monanema and its presence in vector ticks does not impact the burden of B. burgdorferi. We did not detect IgG antibodies to this agent in 127 of 128 sera from patients with Lyme disease or babesiosis. One sample had reactivity above the threshold, but at the low-level equivalent to the least reactive onchocerciasis sera. This low positive signal could be a result of cross-reacting antibodies, antibodies from a previous infection with a filarial nematode, or, less likely, a exposure to the Ixodes scapularis-associated nematode. Conclusions: We found no evidence that this nematode contributes to the spectrum of human tick-borne infections.
Increased salt tolerance in Zymomonas mobilis strain generated by adaptative evolution
Authors: Fuchino Katsuya , Bruheim Per
Published: July 2020

Background Ethanologenic alphaproteobacterium Zymomonas mobilis has been acknowledged as a promising biofuel producer. There have been numerous efforts to engineer this species applicable for an industrial-scale bioethanol production. Although Z. mobilis is robustly resilient to certain abiotic stress such as ethanol, the species is known to be sensitive to saline stress at a mild concentration, which hampers its industrial use as an efficient biocatalyst. To overcome this issue, we implemented a laboratory adaptive evolution approach to obtain salt tolerant Z. mobilis strain.Results During an adaptive evolution, we biased selection by cell morphology to exclude stressed cells. The evolved strains significantly improved growth and ethanol production in the medium supplemented with 0.225 M NaCl. Furthermore, comparative metabolomics revealed that the evolved strains did not accumulate prototypical osmolytes, such as proline, to counter the stress during their growth. The sequenced genomes of the studied strains suggest that the disruption of ZZ6_1149 encoding carboxyl-terminal protease was likely responsible for the improved phenotype.Conclusions The present work successfully generated strains able to grow and ferment glucose under the saline condition that severely perturbs parental strain physiology. Our approach to generate strains, cell shape-based diagnosis and selection, might be applicable to other kinds of strain engineering in Z. mobilis.
Birth weight and renal markers in children aged 5 – 10 years in Cameroon: A cross-sectional study
Authors: Kaze Francois Folefack , Nguefack Seraphin , Asong Constantine Menkoh , Assob Jules Clement Nguedia , Nansseu Jobert Richie , Kowo Mathurin Pierre , Nzana Victorine , Kalla Ginette Claude Mireille , Halle Marie Patrice
Published: July 2020

Background A relationship exists between birth weight (BW) and glomerular filtration rate (GFR) in postnatal kidney. Willing to fill a gap of knowledge in sub-Saharan Africa, we assessed the effect of BW on blood pressure (BP), proteinuria and GFR among Cameroonians children.Methods This was a cross-sectional hospital-based study from January to April 2018 at the Yaounde Gynaeco-Obstetric and Paediatric Hospital (YGOPH). We recruited low BW (LBW) [<2500g], normal BW (NBW) [2500-3999g] and high BW (HBW) [>4000g] children, aged 5-10 years, born and followed-up at YGOPH. We collected socio-demographic, clinical (weight, height, BP), laboratory (proteinuria, creatinine), maternal and birth data. The estimated GFR was calculated using the Schwartz equation.Results We included 80 children (61.2% boys) with 21 (26.2%) LBW, 45 (56.2%) NBW and 14 (15.5%) HBW; the median (interquartile range) age was 7.3 (6.3-8.1) years and 17 (21.2%) were overweight/obese. Two (2.5%) children, all with a NBW (4.4%), had an elevated BP whereas 2 (2.5%) other children, all with a LBW (9.5%), had hypertension (p=0.233). Seven (8.7%) children had proteinuria with 19%, 2.2% and 14.3% having LBW, NBW and HBW, respectively (p=0.051). Equivalent figures were 18 (22.5%), 14.3%, 24.2% and 28.6% for decreased GFR, respectively (p=0.818). There was a trend towards an inverse relationship between BW and BP, proteinuria and GFR (p>0.05). Conclusion Proteinuria is more pronounced in childhood with a history of LBW and HBW while LBW children are more prone to develop hypertension. Regular follow-up is needed to implement early nephroprotective measures among children with abnormal BW.
Lung ultrasound score to determine the effect of fraction inspired oxygen during alveolar recruitment on absorption atelectasis in laparoscopic surgery: A randomized controlled trial
Authors: Kim Bo Rim , Lee Seohee , Bae Hansu , Lee Minkyoo , Bahk Jae-Hyon , Yoon Susie
Published: July 2020

Background: Although the intraoperative alveolar recruitment maneuver (RM) efficiently treats atelectasis, the effect of Fio2 on atelectasis during RM is uncertain. We hypothesized that a high Fio2 (1.0) during RM would lead to a higher degree of postoperative atelectasis without benefiting oxygenation when compared to low Fio2 (0.4). Methods: In this randomized controlled trial, patients undergoing elective laparoscopic surgery in the Trendelenburg position were allocated to low- (Fio2 0.4, n=44) and high-Fio2 (Fio2 1.0, n=46) groups. RM was performed 1-min post tracheal intubation and post changes in supine and Trendelenburg positions during surgery. We set the intraoperative Fio2 at 0.4 for both groups and calculated the modified lung ultrasound score (LUSS) to assess lung aeration after anesthesia induction and at surgery completion. The primary outcome was modified LUSS at the end of the surgery. The secondary outcomes were the intra- and postoperative Pao2 to Fio2 ratio and postoperative pulmonary complications. Results: The modified LUSS before capnoperitoneum and RM (P=0.747) were similar in both groups. However, the postoperative modified LUSS was significantly lower in the low Fio2 group (median difference 5.0, 95% CI 3.0‒7.0, P<0.001). Postoperatively, substantial atelectasis was more common in the high-Fio2 group (relative risk 1.77, 95% CI 1.27‒2.47, P<0.001). Intra- and postoperative Pao2 to Fio2 were similar with no postoperative pulmonary complications. Atelectasis occurred more frequently when RM was performed with high than with low Fio2; oxygenation was not benefitted by a high-Fio2.Conclusions: In patients undergoing laparoscopic surgery in the Trendelenburg position, absorption atelectasis occurred more frequently with high rather than low Fio2. No oxygenation benefit was observed in the high-Fio2 group. Trial registration: ClinicalTrials.gov, NCT03943433. Registered 7 May 2019, https://clinicaltrials.gov/ct2/show/NCT03943433
Efficient 2,3-butanediol production from whey powder using metabolically engineered Klebsiella oxytoca
Authors: Meng Wensi , Zhang Yongjia , Cao Menghao , Zhang Wen , Lü Chuanjuan , Yang Chunyu , Gao Chao , Xu Ping , Ma Cuiqing
Published: July 2020

Background: Whey is a major pollutant generated by the dairy industry. To decrease environmental pollution caused by the industrial release of whey, new prospects for its utilization need to be urgently explored. Here, we investigated the possibility of using whey powder to produce 2,3-butanediol (BDO), an important platform chemical. Results: Klebsiella oxytoca strain PDL-0 was selected because of its ability to efficiently produce BDO from lactose, the major fermentable sugar in whey. After deleting genes pox , pta , frdA , ldhD , and pflB responding for the production of by-products acetate, succinate, lactate, and formate, a recombinant strain K. oxytoca PDL-K5 was constructed. Fed-batch fermentation using K. oxytoca PDL-K5 produced 74.9 g/L BDO with a productivity of 2.27 g/L/h and a yield of 0.43 g/g from lactose. In addition, when whey powder was used as the substrate, 65.5 g/L BDO was produced within 24 h with a productivity of 2.73 g/L/h and a yield of 0.44 g/g. Conclusion: This study demonstrated the efficiency of K. oxytoca PDL-0 for BDO production from whey. Due to its non-pathogenicity and efficient lactose utilization, K. oxytoca PDL-0 might also be used in the production of other important chemicals using whey as the substrate.
Prevalence and abundance of selected genes conferring macrolide resistance genes in COPD patients during maintenance treatment with azithromycin
Authors: Talman Sander , Djamin Remco S. , Schrauwen Eefje J.A. , von Wintersdorff Christian J.H. , Wolffs Petra F. , Savelkoul Paul H.M. , Uzun Sevim , Kerstens René , Eerden Menno M. van der , Kluytmans Jan A.J.W.
Published: July 2020

Objectives: Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients. A major concern with prolonged treatment with antibiotics is the development of bacterial resistance. In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients.Methods: This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period. In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period.Results: There was no increased risk for acquisition of macrolide resistance genes in the azithromycin group compared to the placebo group in COPD patients. However, loss of the macrolide resistance gene ermB was increased overtime in the placebo treated group compared to the azithromycin group (n=5 for the placebo group versus n=0 for the azithromycin group at 12 months; p=0.012). The change in relative abundance of the three macrolide-resistance genes showed that all but one (ermF) increased during treatment with azithromycin. Conclusions: The acquisition rate of macrolide resistance genes in COPD patients treated with azithromycin maintenance therapy was limited, but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo.This study was part of the COLUMBUS trial (Clinicaltrials.gov, NCT00985244).
miR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeting XIAP
Authors: Wang Yuejiao , Zhang Kailin , Yuan Xiaowei , Xu Neili , Zhao Shuai , Hou Linxin , Yang Lili , Zhang Ning
Published: July 2020

Background miR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer. However, its role in fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) remains to be understood. Methods Quantitative real-time polymerase chain reaction was used to detect the relative expression of miR-431-5p in synovial tissues and FLSs. Cell proliferation assays helped examine RA FLS proliferation. Flow cytometry was performed to determine apoptosis and cell cycle progression in RA FLSs. We used dual-luciferase assays to determine the correlation between miR-431-5p and its putative target, X-linked inhibitor of apoptosis (XIAP). Quantitative real-time PCR and western blotting were used to measure XIAP levels in synovial tissues and transfected RA FLSs. Results miR-431-5p was downregulated in synovial tissues and FLSs of patients with RA. Upregulation of miR-431-5p prohibited cell proliferation and the G0/G1-to-S phase transition, but promoted apoptosis in RA FLSs; while miR-431-5p inhibition showed the opposite results. miR-431-5p directly targeted XIAP in RA FLSs, and reversely correlated with XIAP levels in synovial tissues. Notably, XIAP silencing partially restored the effects of miR-431-5p inhibition in RA FLSs. Conclusion miR-431-5p regulates cell proliferation, apoptosis，and cell cycle of RA FLSs by targeting XIAP, suggesting its potential in the treatment of RA.
Scientific Globalism During A Global Crisis:Research Collaboration and Open Access Publications on COVID-19
Authors: Lee Jenny J. , Haupt John P.
Published: July 2020

This study sought to understand the nature of scientific globalism during a global crisis, particularly COVID-19. Findings show that scientific globalism occurs differently when comparing COVID-19 publications with non-COVID-19 publications during as well as before the pandemic. Despite the tense geopolitical climate, countries increased their proportion of international collaboration and open access publications during the pandemic. However, not all countries engaged more globally. Countries that have been more impacted by the crisis and those with relatively lower GDPs tended to participate more in scientific globalism than their counterparts.
What is the Impact of Novel Coronavirus Disease 2019 Pandemic on Orthopedic Surgeons?: Experience from a Single Institution of South Korea
Authors: Kim Gi Beom , Shon Oog-Jin , Park Jeong Jin , Lee Sun-Mi , Lee Gun Woo
Published: July 2020

Background: This study aimed to investigate the cancellation rate and trend of orthopedic surgery at the main institution in Daegu, Korean epicenter of novel coronavirus disease 19 (COVID-19), and to analyze the psychologic status of the healthcare workers in the orthopedic division during the COVID-19 pandemic. Moreover, we sought to assess the outcomes of the preventive surgeries underwent in patients suspected to have COVID-19.Methods: Cancellation rates of elective surgeries over three months since the first confirmed COVID-19 case in South Korea on January 20, 2020 were investigated. Moreover, the number of elective surgeries conducted in the same period over the last two years was compared. Four different questionnaires were used to investigate psychologic impact among health care workers in the orthopedic department. The surveyed outcomes according to occupation and type of work were compared. Urgent preventive surgeries underwent in patients who could not wait for the results of the COVID-19 diagnosis were also investigated.Results: During the pandemic, spine and hip surgery had relatively lower cancellation rates, and elective surgeries were significantly reduced compared to the same period in the last two years. The surveyed outcomes of the psychological questionnaires were within the normal range and there were no significant differences between groups. After preventive surgeries, the virus did not spread to all medical staff involved.Conclusions: During the COVID-19 pandemic, the cancellation rate of orthopedic elective surgeries was significantly higher than in the same period of the previous year, and was different for each subdivision depending on the degree of pain or disability experienced by the patient. Health care workers in the orthopedic division did not seem to have significant psychological distress; rather, a decrease in workload appears to be a positive factor in their mental health. Preventive surgery performed in specialized facilities did not spread the virus to involved medical staff.
Process evaluation of the Bridging the Age Gap in Breast Cancer decision support intervention cluster randomised trial.
Authors: Burton Maria , Lifford Kate J , Wyld Lynda , Armitage Fiona , Ring Alistair , Nettleship Anthony , Collins Karen , Morgan Jenna , Reed Malcolm WR , Holmes Geoffrey R , Bradburn Mike , Gath Jacqui , Green Tracy , Revill Deirdre , Brain Kate , Edwards Adrian
Published: July 2020

The authors have withdrawn this preprint due to author disagreement.
The Burden of Heart Failure: Physicians’, Patients’, and Caregivers’ Perspectives Using Narrative Medicine
Authors: Testa Marco , Cappuccio Antonietta , Latella Maura , Napolitano Silvia , Milli Massimo , Volpe Massimo , Marini Maria Giulia
Published: July 2020

Background The TRUST (The Roadmap Using Story Telling) project used a Narrative Medicine (NM) framework to assess the impressions of people with heart failure (HF), their informal caregivers and HF specialists of the impact of heart failure (HF) on the daily life of patients and their carers. Methods Italian HF specialists participated on a voluntary basis, completing their own narratives, and inviting patients and their caregivers to write anonymously about their experiences, all on a dedicated online platform. The narratives were analyzed according to standard NM methodology. Results 82 narratives were collected from patients, 61 from caregivers, and 104 from HF specialists. Analysis of the three points of view revealed the extent of the burden of illness on the entire family, particularly that of the caregiver. The impact was mainly experienced as emotional and social limitations in patients’ and their caregivers’ daily lives. The analysis of all three points of view highlighted a strong difference between how HF is perceived by patients, caregivers, and HF specialists. Conclusions This NM project illustrates the complex issues of living with HF and gave new insight into integrating three different perspectives into the HF pathway of care.
The Characteristics of Overseas Imported COVID-19 Cases and the Effectiveness of Screening Strategy in Beijing, China
Authors: Li Li , Ma Cheng-Jie , Chang Yu-Fei , Yang Si-Yuan , Tang Yun-Xia , Wang Linghang
Published: July 2020

Background: In March 2020, the WHO declared the novel coronavirus (COVID-19) outbreak a global pandemic. While great success in the coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategy in Beijing, China.Methods: This retrospective study included all imported COVID-19 cases from Beijing Ditan Hospital from 29 February to 20 March 2020, who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging were collected and analyzed. Results: A total of 71 imported cases were finally diagnosed with laboratory-confirmed COVID-19. The cases were mainly acquired from Europe (63cases, 88.73%). The main clinical manifestations were fever and cough, which accounted for 30 cases (42.25%) and 35 cases (49.30%), respectively. Only 4 cases (5.63%) had lymphocytopenia and 13 (18.31%) cases demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin(PCT). 35 cases (49.30%) had abnormal CT findings at initial presentation, whereas 36 cases (50.70%) had a normal CT. Using RT-PCR, 59 cases (83.10%) were tested positive at initial presentation.Conclusions: The combination of screening tools, particularly CT and RT-PCR, could be considered to improve the diagnosis in imported COVID-19 cases. Our findings provide the important information and clinical evidence for infection control of imported COVID-19 cases.
Effects of canola or olive oil on plasma lipids, lipoprotein-associated phospholipase A2 and inflammatory cytokines in patients referred to coronary angiography
Authors: Khandouzi Nafiseh , Zahedmehr Ali , Nasrollahzadeh Javad
Published: July 2020

Background: The potential cardioprotective benefits of olive oil (OO) and canola oil (CO) consumption have been shown in some studies. The present study was conducted to compare the effects of CO and OO on plasma lipids, some inflammatory cytokines, and lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) mass and activity in patients undergoing coronary angiography. Methods: A randomized, controlled, parallel-arm, clinical trial involving 48 patients (44 men and 4 women, aged 57.63 ± 6.34 years) with at least one classic cardiovascular risk factor (hypertension, dyslipidemia, or diabetes) who referred to coronary angiography was performed. Patients were randomly divided into two groups and received 25 mL/day refined olive oil (n=24) or canola oil (n=24) for 6 weeks. Plasma lipids, some selected inflammatory markers, and Lp-PLA 2 levels were measured at the baseline and after the intervention. Results: CO consumption produced a significant reduction in plasma Lp-PLA 2 mass (-0.97 ± 1.84 vs. 0.34 ± 1.57 ng/mL, P = 0.008 for CO and OO, respectively), whereas the mean changes of Interleukine-6 concentration were significantly lower after OO consumption compared with CO (-9.46 ± 9.46 vs. -0.90 ± 6.80 pg/mL, P = 0.008 for OO and CO, respectively). After 6 weeks of intervention, no significant changes were observed in plasma Lp-PLA 2 activity, complement C3, C4, and lipid profile in two intervention groups. Conclusions: Comparing the two vegetable oils in subjects with cardiovascular risk factors shows that consumption of olive oil is more effective in reducing the level of inflammatory cytokine Interleukine-6 whereas canola oil is more effective in lowering the level of Lp-PLA 2 .
Integrative transcriptome analyses empower the anti-COVID-19 drug arsenal
Authors: El-Hachem Nehme , Eid Edward , Nemer Georges , Dbaibo Ghassan , Abbas Ossama , Rubeiz Nelly , Zeineldine Salah , Matar Ghassan M. , Bikorimana Jean-Pierre , Shammaa Riam , Haibe-Kains Benjamin , Kurban Mazen , Rafei Moutih
Published: July 2020

The beginning of the twenty-first century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The current pandemic COVID-19 (Coronavirus disease 2019) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a rapid infection rate, it is a global threat endangering the livelihoods of millions worldwide. Currently, and despite the collaborative efforts of governments, researchers, and the pharmaceutical industries, there are no substantially significant treatment protocols for the disease. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression profiles from normal lung transcriptomes. Our unbiased systems biology approach not only shed light on previously unexplored molecular details of SARS-CoV-2 infection (e.g., interferon signaling, inflammation and ACE2 co-expression hallmarks in normal and infected lungs) but most importantly prioritized more than 50 repurposable drug candidates (e.g., Corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA approved candidates as monotherapy or in combination with an antiviral regimen (e.g., Remdesivir) could lead to promising outcomes in COVID-19 patients.
Complex yeast-bacteria interactions affect the yield of industrial ethanol fermentations
Authors: Lino Felipe , Bajic Djordje , Vila Jean , Sanchez Alvaro , Sommer Morten
Published: July 2020

Microbial communities affect several natural processes, from nutrient cycling to human health. Nevertheless, the mechanisms of interaction between microorganisms and their influence on community functions are not well understood. Sugarcane ethanol fermentations represent a simple microbial community dominated by S. cerevisiae and co-occurring bacteria with a clearly defined functionality. In this study, we dissected the microbial interactions in sugarcane ethanol fermentation by combinatorically reconstituting every possible combination of species, comprising approximately 80% of the biodiversity in terms of relative abundance. Functional landscape analysis showed that higher-order interactions counterbalance the negative effect of pairwise interactions on ethanol yield. In addition, we found that Lactobacillus amylovorus improves the yeast growth rate and ethanol yield by cross-feeding acetaldehyde, as shown by flux balance analysis and laboratory experiments. Our results suggest that Lactobacillus amylovorus could be considered an industrial probiotic with the potential to improve sugarcane ethanol fermentation yields by more than 10%. These data highlight the biotechnological importance of comprehensively studying microbial communities and could be extended to other microbial systems with relevance to human health and the environment.
Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways
Authors: Kim Woo Seok , Hong Sungcheol , Gamero Milenka , Jeevakumar Vivekanand , Smithhart Clay , Price Theodore , Campos Carlos , Palmiter Richard , Park Sung Il
Published: July 2020

The vagus nerve supports diverse autonomic functions and behaviors important for health and survival. To understand how specific components of the vagus contribute to behaviors and long-term physiological effects, it is critical to modulate their activity with anatomical specificity in awake, freely behaving conditions using reliable methods. Here, we introduce an organ-specific scalable, multimodal, wireless optoelectronic device for precise and chronic optogenetic manipulations in vivo. When combined with an advanced, coil-antenna system and a multiplexing strategy for powering 8 individual homecages using a single RF transmitter, the proposed wireless telemetry enables low cost, high-throughput, and precise functional mapping of peripheral neural circuits, including long-term behavioral and physiological measurements. Deployment of these technologies revealed an unexpected role for stomach, non-stretch vagal sensory fibers in suppressing appetite and demonstrated the durability of the miniature wireless device inside harsh gastric conditions.
Clinical Characteristics and Laboratory Biomarkers Changes in COVID-19 Patients Requiring or not Intensive or Sub-Intensive Care: A Comparative Study
Authors: Cattelan Anna Maria , Meco Eugenia Di , Trevenzoli Marco , Frater Alessia , Ferrari Anna , Villano Marco , Gomiero Federica , Carretta Giovanni , Sasset Lolita
Published: July 2020

BackgroundIdentifying risk factors for severe novel-coronavirus disease (COVID-19) is essential to ascertain which patients may benefit from advanced supportive care. The study aims to give a comparative description of COVID-19 patients who were admitted or not to the intensive (ICU) or sub-intensive cares units (SICU). MethodsThis observational study of prospectively collected data included all COVID-19 patients primarily admitted to the Infectious Diseases department of Padua between February 22 and May 20, 2020. Clinical, laboratory, radiological and treatment data were collected. The primary outcome was a composite of ICU and/or SICU admission. Results 303 patients were included. Median age was 62 years (IQR:50-74), 60.1% were male. 234 patients were managed in the Infectious Diseases ward (Group 1) and 69 patients (22,8%) met the primary outcome (Group 2). The mortality rate was 6.8%. Group 2 were more likely to be men, had a higher mortality (14,5%vs3,8%, p<0,01) and had more hypertension (72,4vs 44%,p<0,01) and diabetes (31,9vs21%,p=0,04). Chest X-ray at admission was positive in 63,2% and Group 2 were more likely to develop pathological findings during the hospitalization (72,7%vs17,2%,p<0,01). Group 2 presented at admission a higher neutrophil count, aspartate-transaminase and C-reactive-protein. At the 3° measurement, differences were found for white blood cell and neutrophil count, liver function tests and C-reactive-protein. Group 1 presented a shorter duration from admission to negativization of follow-up swabs (20vs35days,p<0,01). ConclusionsThe presence of comorbidities and the persistent observation of slightly abnormal laboratory findings should be regarded as predisposing factors for disease severity and clinical worsening.
Near Field Condensation
Authors: Yan Xiao , Chen Feipeng , Zhao Chongyan , Qin Yimeng , Wang Xiong , Rabbi Kazi Fazle , Hoque Muhammad Jahidul , Zhao Hanyang , Li Jiaqi , Gebrael Tarek , Chen Feng , Feng Jie , Miljkovic Nenad
Published: July 2020

Dropwise condensation represents the upper limit of condensation heat transfer. Promoting dropwise condensation relies on surface chemical functionalization, and is fundamentally limited by the maximum droplet departure size. A century of research has focused on active and passive methods to enable the removal of ever smaller droplets. However, fundamental contact line pinning limitations prevent gravitational and shear-based removal of droplets smaller than 250 µm. Here, we break this limitation through near field condensation. By de-coupling nucleation, droplet growth, and shedding via droplet transfer between parallel surfaces, we enable the control of droplet population density and removal of droplets as small as 20 µm without the need for chemical modification or surface structuring. We identify droplet bridging to develop a regime map, showing that rational wettability contrast propels spontaneous droplet transfer from condensing surfaces ranging from hydrophilic to hydrophobic. To demonstrate efficacy, we perform condensation experiments on surfaces ranging from hydrophilic to superhydrophobic. The results show that near field condensation with optimal gap spacing can limit the maximum droplet sizes and significantly increase the population density of sub-20 µm droplets. Theoretical analysis and direct numerical simulation confirm the breaking of classical condensation heat transfer paradigms through enhanced heat transfer. Our study not only pushes beyond century-old phase change limitations, it demonstrates a promising method to enhance the efficiency of applications where high, tunable, gravity-independent, and durable condensation heat transfer is required.