bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory Syncytial Virus Replication Is Promoted by Autophagy-Mediated Inhibition of Apoptosis
Authors: Li Miao , Li Jian , Zeng Ruihong , Yang Jianling , Liu Jianguo , Zhang Zhengzheng , Song Xiaotian , Yao Zhiyan , Ma Cuiqing , Li Wenjian , Wang Kai , Wei Lin 
Published: January 2018

ABSTRACT

Respiratory syncytial virus (RSV) is the main cause of acute lower respiratory tract infection (ALRI) in children worldwide. Virus-host interactions affect the progression and prognosis of the infection. Autophagy plays important roles in virus-host interactions. Respiratory epithelial cells serve as the front line of host defense during RSV infection, However, it is still unclear how they interact with RSV. In this study, we found that RSV induced autophagy that favored RSV replication and exacerbated lung pathology
in vivo
. Mechanistically, RSV induced complete autophagy flux through reactive oxygen species (ROS) generation and activation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK-MTOR) signaling pathway in HEp-2 cells. Furthermore, we evaluated the functions of autophagy in RSV replication and found that RSV replication was increased in HEp-2 cells treated with rapamycin but decreased remarkably in cells treated with 3-methylademine (3-MA) or wortmannin. Knockdown key molecules in the autophagy pathway with short hairpinp RNA (shRNA) against autophagy-related gene 5 (
ATG5
), autophagy-related gene 7 (
ATG7
), or
BECN1/Beclin 1
or treatment with ROS scavenger N-acetyl-
l
-cysteine (NAC) and AMPK inhibitor (compound C) suppressed RSV replication. 3-MA or sh
ATG5/BECN1
significantly decreased cell viability and increased cell apoptosis at 48 hours postinfection (hpi). Blocking apoptosis with Z-VAD-FMK partially restored virus replication at 48 hpi. Those results provide strong evidence that autophagy may function as a proviral mechanism in a cell-intrinsic manner during RSV infection.

IMPORTANCE
An understanding of the mechanisms that respiratory syncytial virus utilizes to interact with respiratory epithelial cells is critical to the development of novel antiviral strategies. In this study, we found that RSV induces autophagy through a ROS-AMPK signaling axis, which in turn promotes viral infection. Autophagy favors RSV replication through blocking cell apoptosis at 48 hpi. Mechanistically, RSV induces mitophagy, which maintains mitochondrial homeostasis and therefore decreases cytochrome
c
release and apoptosis induction. This study provides a novel insight into this virus-host interaction, which may help to exploit new antiviral treatments targeting autophagy processes.
Modifications to the Foot-and-Mouth Disease Virus 2A Peptide: Influence on Polyprotein Processing and Virus Replication
Authors: Kjær Jonas , Belsham Graham J. 
Published: January 2018

ABSTRACT

Foot-and-mouth disease virus (FMDV) has a positive-sense single-stranded RNA (ssRNA) genome that includes a single, large open reading frame encoding a polyprotein. The cotranslational “cleavage” of this polyprotein at the 2A/2B junction is mediated by the 2A peptide (18 residues in length) using a nonproteolytic mechanism termed “ribosome skipping” or “StopGo.” Multiple variants of the 2A polypeptide with this property among the picornaviruses share a conserved C-terminal motif [D(V/I)E(S/T)NPG↓P]. The impact of 2A modifications within this motif on FMDV protein synthesis, polyprotein processing, and virus viability were investigated. Amino acid substitutions are tolerated at residues E
14
, S
15
, and N
16
within the 2A sequences of infectious FMDVs despite their reported “cleavage” efficiencies at the 2A/2B junction of only ca. 30 to 50% compared to that of the wild type (wt). In contrast, no viruses containing substitutions at residue P
17
, G
18
, or P
19
, which displayed little or no “cleavage” activity
in vitro
, were rescued, but wt revertants were obtained. The 2A substitutions impaired the replication of an FMDV replicon. Using transient-expression assays, it was shown that certain amino acid substitutions at residues E
14
, S
15
, N
16
, and P
19
resulted in partial “cleavage” of a protease-free polyprotein, indicating that these specific residues are not essential for cotranslational “cleavage.” Immunofluorescence studies, using full-length FMDV RNA transcripts encoding mutant 2A peptides, indicated that the 2A peptide remained attached to adjacent proteins, presumably 2B. These results show that efficient “cleavage” at the 2A/2B junction is required for optimal virus replication. However, maximal StopGo activity does not appear to be essential for the viability of FMDV.

IMPORTANCE
Foot-and-mouth disease virus (FMDV) causes one of the most economically important diseases of farm animals. Cotranslational “cleavage” of the FMDV polyprotein precursor at the 2A/2B junction, termed StopGo, is mediated by the short 2A peptide through a nonproteolytic mechanism which leads to release of the nascent protein and continued translation of the downstream sequence. Improved understanding of this process will not only give a better insight into how this peptide influences the FMDV replication cycle but may also assist the application of this sequence in biotechnology for the production of multiple proteins from a single mRNA. Our data show that single amino acid substitutions in the 2A peptide can have a major influence on viral protein synthesis, virus viability, and polyprotein processing. They also indicate that efficient “cleavage” at the 2A/2B junction is required for optimal virus replication. However, maximal StopGo activity is not essential for the viability of FMDV.
Morbidity and mortality with early pulmonary haemorrhage in preterm neonates
Authors: Ahmad Kaashif Aqeeb , Bennett Monica Michelle , Ahmad Samiya Fatima , Clark Reese Hunter , Tolia Veeral Nalin 
Published: January 2018

ObjectiveThere are no large studies evaluating pulmonary haemorrhage (PH) in premature infants. We sought to quantify the clinical characteristics, morbidities and mortality associated with early PH.DesignData were abstracted from the Pediatrix Clinical Data Warehouse, a large de-identified data set. For incidence calculations, we included infants from 340 Pediatrix United States Neonatal Intensive Care Units from 2005 to 2014 without congenital anomalies. Infants <28 weeks’ gestation with PH within 7 days of birth were then matched with two controls for birth weight, gestational age, gender, antenatal steroid exposure, day of life 0 or 1 intubation and multiple gestation.ResultsFrom 596 411 total infants, we identified 2799 with a diagnosis of PH. Peak incidence was 86.9 cases per 1000 admissions for neonates born at 24 weeks’ gestation. We then identified 1476 infants <28 weeks’ gestation with an early PH diagnosis at ≤7 days of age of which 1363 (92.3%) were successfully matched. Patients with early PH had significantly higher exposure to poractant alfa (35.4% vs 28%), diagnosis of shock (63.7% vs 51%) and grade IV intraventricular haemorrhage (20.8% vs 6%). Patients with PH also had significantly higher mortality rates at 7 days of age (40.6% vs 18.9%), 30 days of age (54% vs 28.8%) and prior to discharge (56.9% vs 33.7).ConclusionIn this large cohort of premature infants, we found PH to be common among the most premature babies. Early PH was associated with significant morbidity and mortality in excess of 50%. A renewed focus on the underlying pathophysiology and prevention of PH is warranted.
Severity and burden of hand, foot and mouth disease in Asia: a modelling study
Authors: Koh Wee Ming , Badaruddin Hishamuddin , La Hanh , Chen Mark I-Cheng , Cook Alex R 
Published: January 2018

BackgroundHand, foot and mouth disease (HFMD) affects millions of children across Asia annually, leading to an increase in implemented control policies such as surveillance, isolation and social distancing in affected jurisdictions. However, limited knowledge of disease burden and severity causes difficulty in policy optimisation as the associated economic cost cannot be easily estimated. We use a data synthesis approach to provide a comprehensive picture of HFMD disease burden, estimating infection risk, symptomatic rates, the risk of complications and death, and overall disability-adjusted life-year (DALY) losses, along with associated uncertainties.MethodsComplementary data from a variety of sources were synthesised with mathematical models to obtain estimates of severity of HFMD. This includes serological and other data extracted through a systematic review of HFMD epidemiology previously published by the authors, and laboratory investigations and sentinel reports from Singapore’s surveillance system.ResultsHFMD is estimated to cause 96 900 (95% CI 40 600 to 259 000) age-weighted DALYs per annum in eight high-burden countries in East and Southeast Asia, with the majority of DALYs attributed to years of life lost. The symptomatic case hospitalisation rate of HFMD is 6% (2.8%–14.9%), of which 18.7% (6.7%–31.5%) are expected to develop complications. 5% (2.9%–7.4%) of such cases are fatal, bringing the overall case fatality ratio to be 52.3 (24.4–92.7) per 100 000 symptomatic infections. In contrast, the EV-A71 case fatality ratio is estimated to be at least 229.7 (75.4–672.1) per 100 000 symptomatic cases. Asymptomatic rate for EV-A71 is 71.4% (68.3%–74.3%) for ages 1–4, the years of greatest incidence.ConclusionDespite the high incidence rate of HFMD, total DALY due to HFMD is limited in comparison to other endemic diseases in the region, such as dengue and upper respiratory tract infection. With the majority of DALY caused by years of life lost, it is possible to mitigate most with increased EV-A71 vaccine coverage.
Thread embedding acupuncture for musculoskeletal pain: a systematic review and meta-analysis protocol
Authors: Cho Yeeun , Lee Seunghoon , Kim Jihye , Kang Jung Won , Lee Jae-Dong 
Published: January 2018

IntroductionThread embedding acupuncture (TEA) is a special type of acupuncture that inserts certain medical threads (eg, catgut or polydioxanone) into subcutaneous tissue or muscles at specific points. Although TEA has been widely used for the treatment of musculoskeletal pain in Korea, China and Taiwan, evidence regarding its efficacy is lacking. The aim of this protocol is to evaluate the effectiveness and safety of TEA in the treatment of musculoskeletal pain, by conducting a systematic review and meta-analysis.Methods and analysisThe following 16 databases will be searched from their inception to 14 May 2017: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, three Chinese database (China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database and the Wanfang database) and eight Korean databases (Korean Medical Database, Korean Association of Medical Journal Editors, Korean Studies Information Service System, Korean National Assembly Digital Library, National Digital Science Library, Oriental Medicine Advanced Searching Integrated System, ’Database Periodical Information Academic and Korean Traditional Knowledge Portal'). The WHO International Clinical Trials Registry Platform will also be searched to retrieve the recently completed studies.All randomised controlled studies in which TEA was used on specific points for the treatment of musculoskeletal pain will be included and no restrictions on language will be applied. The risk of bias of each study will be evaluated by the Cochrane risk of bias tool.Mean difference or standardised mean difference for continuous data and risk ratio for dichotomous data will be calculated with 95% CIs using a random effects model or a fixed effects model. Additional subgroup and sensitivity analyses will be conducted according to a predefined protocol.Ethics and disseminationNo ethical issues are predicted. The systematic review will be published in a peer-reviewed journal or conference presentation. These findings will summarise the current evidence of TEA for the treatment of musculoskeletal pain and may provide guidance for clinicians and patients to select TEA for musculoskeletal pain.PROSPERO registration numberCRD42015019046.
Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction: a nationwide population-based, propensity-matched cohort study in Taiwan
Authors: Kuo Shu-Hung , Hung Wang-Ting , Tang Pei-Ling , Huang Wei-Chun , Yang Jin-Shiou , Lin Hsiao-Chin , Mar Guang-Yuan , Chang Hong-Tai , Liu Chun-Peng 
Published: January 2018

IntroductionThe influence of hepatitis C virus (HCV) infection on long-term outcomes of patients with acute myocardial infarction (AMI) is unclear. Therefore, this study aimed to analyse the impact of HCV infection on 12-year mortality rates after AMI using data from the Taiwan National Health Insurance Research Database (NHIRD).MethodsNHIRD data for approximately 23 000 000 patients between January 2000 and December 2012 were analysed. A total of 186 112 cases of first AMI admission were identified. A total of 4659 patients with HCV infection not receiving interferon therapy were enrolled and divided into those with (n=107) or without (n=4552) cirrhosis. Using one-to-one matching, 4552 matched controls were included in the final analysis.ResultsThe 12-year mortality rate was significantly higher in patients with AMI with HCV infection and cirrhosis than in those with HCV infection but without cirrhosis (P<0.0001) or controls (P<0.0001). Patients with HCV infection but without cirrhosis had significantly higher long-term mortality rates than the matched controls (P<0.0001). The HR for mortality was higher in patients with HCV infection (HR 1.12; 95% CI 1.06 to 1.18). HCV influenced outcomes among the subgroups of patients who were male (HR 1.15) and those who had hypertension (HR 1.14).ConclusionsHCV infection influenced the 12-year mortality rates of patients with AMI, especially those who were male and those who had hypertension. Cirrhosis further increased the long-term mortality rates of patients with AMI with HCV infection.
Multicentre validation of a sepsis prediction algorithm using only vital sign data in the emergency department, general ward and ICU
Authors: Mao Qingqing , Jay Melissa , Hoffman Jana L , Calvert Jacob , Barton Christopher , Shimabukuro David , Shieh Lisa , Chettipally Uli , Fletcher Grant , Kerem Yaniv , Zhou Yifan , Das Ritankar 
Published: January 2018

ObjectivesWe validate a machine learning-based sepsis-prediction algorithm (InSight) for the detection and prediction of three sepsis-related gold standards, using only six vital signs. We evaluate robustness to missing data, customisation to site-specific data using transfer learning and generalisability to new settings.DesignA machine-learning algorithm with gradient tree boosting. Features for prediction were created from combinations of six vital sign measurements and their changes over time.SettingA mixed-ward retrospective dataset from the University of California, San Francisco (UCSF) Medical Center (San Francisco, California, USA) as the primary source, an intensive care unit dataset from the Beth Israel Deaconess Medical Center (Boston, Massachusetts, USA) as a transfer-learning source and four additional institutions’ datasets to evaluate generalisability.Participants684 443 total encounters, with 90 353 encounters from June 2011 to March 2016 at UCSF.InterventionsNone.Primary and secondary outcome measuresArea under the receiver operating characteristic (AUROC) curve for detection and prediction of sepsis, severe sepsis and septic shock.ResultsFor detection of sepsis and severe sepsis,InSightachieves an AUROC curve of 0.92 (95% CI 0.90 to 0.93) and 0.87 (95% CI 0.86 to 0.88), respectively. Four hours before onset,InSightpredicts septic shock with an AUROC of 0.96 (95% CI 0.94 to 0.98) and severe sepsis with an AUROC of 0.85 (95% CI 0.79 to 0.91).ConclusionsInSightoutperforms existing sepsis scoring systems in identifying and predicting sepsis, severe sepsis and septic shock. This is the first sepsis screening system to exceed an AUROC of 0.90 using only vital sign inputs.InSightis robust to missing data, can be customised to novel hospital data using a small fraction of site data and retains strong discrimination across all institutions.
Evaluating sickness absence duration by musculoskeletal and mental health issues: a retrospective cohort study of Scottish healthcare workers
Authors: Demou Evangelia , Smith Shanley , Bhaskar Abita , Mackay Daniel F , Brown Judith , Hunt Kate , Vargas-Prada Sergio , Macdonald Ewan B 
Published: January 2018

ObjectivesSickness absence (SA) among healthcare workers is associated with occupational and non-occupational risk factors and impacts employee health, healthcare delivery and patient health. At the same time, healthcare is one of the employment sectors with the highest rates of work-related ill health in the UK. Musculoskeletal (MSK) and mental health (MH) issues are leading causes of SA, but there is a lack of research on how certain MSK/MH conditions impact on SA duration. The study aim is to determine differences in SA duration by MH and MSK disorders in healthcare employees.MethodsSurvival analyses were used to estimate SA duration due to MSK and MH problems over 6 years, and Cox’s proportional hazards models to determine the HRs of returning to work, using a bespoke Scottish health board database with over 53 000 SA events. SA duration and time to return-to-work (RTW) were estimated for employees by age, gender, job and health conditions.ResultsMSK and MH conditions accounted for 27% and 6% of all SA events and 23.7% and 19.5% of all days lost, respectively. Average SA duration was 43.5 days for MSK and 53.9 days for MH conditions. For MSK conditions, employees with low back or neck pain had the fastest RTW (median P50: 7 days), whereas employees absent due to depression took the longest (P50: 54 days). The most influential sociodemographic variables affecting RTW were age, gender and job category.ConclusionsUsing a unique and rich database, we found significant differences in SA duration by presenting condition in healthcare workers. MH conditions, and depression specifically, accounted for the most working days’ absence. Significant variations in duration were also observed for MSK conditions. Our findings can inform public health practitioners and healthcare managers of the most significant factors impacting MSK-related and MH-related SA to develop and implement tailored and targeted workplace interventions.
Cross-sectional study assessing the addition of contrast sensitivity to visual acuity when testing for fitness to drive
Authors: Spreng Lucie , Favrat Bernard , Borruat François-Xavier , Vaucher Paul 
Published: January 2018

ObjectivesThe aim of this study is to quantify the importance of loss of contrast sensitivity (CS) and its relationship to loss of visual acuity (VA), driving restrictions and daytime, on-road driving evaluations in drivers aged 70+.DesignA predictive cross-sectional study.SettingVolunteer participants to a drivers’ refresher course for adults aged 70+ delivered by the Swiss Automobile Club in western Switzerland from 2011 to 2013.Participants162 drivers, male and female, aged 70 years or older.Clinical predictorsWe used a vision screener to estimate VA and the The Mars Letter Contrast Sensitivity Test to test CS.OutcomesWe asked drivers to report whether they found five driving restrictions useful for their condition; restrict driving to known roads, avoid driving on highways, avoid driving in the dark, avoid driving in dense traffic and avoid driving in fog. All participants also underwent a standardised on-road evaluation carried out by a driving instructor.ResultsModerate to severe loss of CS for at least one eye was frequent (21.0% (95% CI 15.0% to 28.1%)) and often isolated from a loss of VA (11/162 cases had a VA ≥0.8 decimal and a CS of ≤1.5 log(CS); 6.8% (95% CI 3.4% to 11.8%)). Drivers were more likely (R2=0.116, P=0.004) to report a belief that self-imposed driving restrictions would be useful if they had reduced CS in at least one eye. Daytime evaluation of driving performance seems limited in its ability to correctly identify difficulties related to CS loss (VA: R2=0.004, P=0.454; CS: R2=0.006, P=0.332).ConclusionCS loss is common for older drivers. Screening CS and referring for cataract surgery even in the absence of VA loss could help maintain mobility. Reduced CS and moderate reduction of VA were both poor predictors of daytime on-road driving performances in this research study.
Students’ satisfaction and perceived impact on knowledge, attitudes and skills after a 2-day course in scientific writing: a prospective longitudinal study in Spain
Authors: Fernández Esteve , García Ana M , Serés Elisabet , Bosch Fèlix 
Published: January 2018

ObjectivesThis study aimed to determine students’ satisfaction with a 2-day course on scientific writing in health sciences and to assess their perceptions of the long-term impact on their knowledge, attitudes and skills.Setting27 iterations of a 2-day course on writing and publishing scientific articles in health sciences.Participants741 students attending the 27 courses.DesignProspective longitudinal study.Primary and secondary outcome measuresImmediately after each course, students completed a first questionnaire, rating their satisfaction with different aspects of the classroom sessions on a Likert scale (0–5). Approximately 2 years after the course, students completed a follow-up questionnaire, using a Likert scale (0–4) to rate their knowledge, skills and attitudes in relation to scientific writing before and after attending the course.Results741 students (70% women) participated in the 27 iterations of the course; 568 (76.8%) completed the first questionnaire and 182 (24.6%) completed the follow-up questionnaire. The first questionnaire reflected high overall satisfaction (mean score, 4.6). In the second questionnaire, students reported that the course had improved their knowledge (mean improvement: 1.6; 95% CI 1.6 to 1.7), attitudes (mean improvement: 1.3; 95% CI 1.2 to 1.4) and skills (mean improvement: 1.4; 95% CI 1.3 to 1.4) related to writing and publishing scientific papers. Most respondents (n=145, 79.7%) had participated in drafting a scientific paper after the course; in this subgroup, all the specific writing skills assessed in the second questionnaire significantly improved.ConclusionsStudents were satisfied with the format and the contents of the course, and those who responded to the follow-up survey considered that the course had improved their knowledge, attitudes and skills in relation to scientific writing and publishing. Courses are particularly important in countries without strong traditions in scientific publication.