bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accounting for biases in survey-based estimates of population attributable fractions
Authors: Masters Ryan , Reither Eric 
Published: December 2019

Abstract
Background
This paper discusses best practices for estimating fractions of mortality attributable to health exposures in survey data that are biased by observed confounders and unobserved endogenous selection. Extant research has shown that estimates of population attributable fractions (PAF) from the formula using the proportion of deceased that is exposed (PAFpd) can attend to confounders, whereas the formula using the proportion of the entire sample exposed (PAFpe) is biased by confounders. Research has not explored how PAFpd and PAFpe equations perform when both confounding and selection bias are present.

Methods
We review equations for calculating PAF based on either the proportion of deceased (pd) or the proportion of the entire sample (pe) that receives the exposure. We explore how estimates from each equation are affected by confounding bias and selection bias using hypothetical data and real-world survey data from the National Health Interview Survey–Linked Mortality Files, 1987–2011. We examine the association between cigarette smoking and all-cause mortality risk in the US adult population as an example.

Results
We show that both PAFpd and PAFpe calculate the true PAF in the presence of confounding bias if one uses the “weighted-sum” approach. We further show that both the PAFpd and PAFpe calculate biased PAFs in the presence of collider bias, but that the bias is more severe in the PAFpd formula.

Conclusion
We recommend that researchers use the PAFpe formula with the weighted-sum approach when estimates of the exposure-outcome relationship are biased by endogenous selection.
NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma
Authors: Zhou Hong-Zhong , Zeng Han-Qing , Yuan Ding , Ren Ji-Hua , Cheng Sheng-Tao , Yu Hai-Bo , Ren Fang , Wang Qing , Qin Yi-Ping , Huang Ai-Long , Chen Juan 
Published: December 2019

Abstract
Background
Our previous study has demonstrated that NAD(P)H: quinone oxidoreductase 1 (NQO1) is significantly upregulated in human liver cancer where it potentiates the apoptosis evasion of liver cancer cell. However, the underlying mechanisms of the oncogenic function of NQO1 in HCC have not been fully elucidated.

Methods
Expression of NQO1, SIRT6, AKT and X-linked inhibitor of apoptosis protein (XIAP) protein were measured by western blotting and immunohistochemistry. Additionally, the interaction between NQO1 and potential proteins were determined by immunoprecipitation assays. Furthermore, the effect of NQO1 and SIRT6 on tumor growth was determined in cell model and orthotopic tumor implantation model.

Results
We found that NQO1 overexpression in HCC enhanced SIRT6 protein stability via inhibiting ubiquitin-mediated 26S proteasome degradation. High level of SIRT6 reduced acetylation of AKT which resulted in increased phosphorylation and activity of AKT. Activated AKT subsequently phosphorylated anti-apoptotic protein XIAP at Ser87 which determined its protein stability. Reintroduction of SIRT6 or AKT efficiently rescued NQO1 knock-out-mediated inhibition of growth and induction of apoptosis. In orthotopic mouse model, NQO1 knock-out inhibited tumor growth and induced apoptosis while this effect was effectively rescued by SIRT6 overexpression or MG132 treatment partially.

Conclusions
Collectively, these results reveal an oncogenic function of NQO1 in sustaining HCC cell proliferation through SIRT6/AKT/XIAP signaling pathway.
Unhealthy snack intake modifies the association between screen-based sedentary time and metabolic syndrome in Brazilian adolescents
Authors: Schaan Camila Wohlgemuth , Cureau Felipe Vogt , Salvo Deborah , Kohl Harold W. , Schaan Beatriz D. 
Published: December 2019

AbstractBackgroundExcessive screen time has been associated with metabolic syndrome (MetS) among adolescents; however, snack intake in front of screens may play a role in this association. Therefore, our objective was to investigate the association between screen-based sedentary time with MetS and whether this association is modified by unhealthy snack intake in front of screens.MethodsThis study was a nationwide, cross-sectional, school-based survey in Brazil including adolescents aged 12 to 17 years. The frequency of snack consumption in front of screen and screen-based sedentary time (TV view, computers and videogames use) were self-reported. Thereafter, screen time was categorized (≤2, 3–5 and ≥ 6 h/day); snack consumption in front of screens was dichotomized. Metabolic syndrome diagnosis was defined based on the International Diabetes Federation criteria. Associations between screen time and MetS were investigated using logistic regression in overall sample and after stratification by snack intake in front of screens.ResultsA total of 33,900 adolescents were included in the analysis. The final adjusted model, which included sociodemographic data, physical activity, and energy intake, showed that adolescents who spent ≥6 h/day in front of screens had an increased odds ratio for MetS (OR = 1.68, 95%CI: 1.03–2.74). However, after stratifying the sample according to reported snack intake, the association between higher screen-based sedentary time and MetS remained significant only for adolescents who reported consumption of snacks in front of screens.ConclusionLonger screen-based sedentary times were directly associated with MetS. However, this association seems to be modified by reported snack intake in front of screens.
Do associations of sex, age and education with transport and leisure-time physical activity differ across 17 cities in 12 countries?
Authors: Mitáš Josef , Cerin Ester , Reis Rodrigo Siqueira , Conway Terry L. , Cain Kelli L. , Adams Marc A. , Schofield Grant , Sarmiento Olga L. , Christiansen Lars B. , Davey Rachel , Salvo Deborah , Orzanco-Garralda Rosario , Macfarlane Duncan , Hino Adriano Akira F. , De Bourdeaudhuij Ilse , Owen Neville , Van Dyck Delfien , Sallis James F. 
Published: December 2019

Abstract
Background
Leisure-time and transport activity domains are studied most often because they are considered more amenable to intervention, but to date evidence on these domains is limited. The aim of the present study was to examine patterns of socio-demographic correlates of adults’ leisure-time and transport physical activity and how these associations varied across 17 cities in 12 countries.

Methods
Participants (N = 13,745) aged 18–66 years in the IPEN Adult study and with complete data on socio-demographic and self-reported physical activity characteristics were included. Participants reported frequency and duration of leisure-time and transport activities in the last 7 days using the self-administered International Physical Activity Questionnaire-Long Form. Six physical activity outcomes were examined in relation with age, education, and sex, and analyses explored variations by city and curvilinear associations.

Results
Sex had the most consistent results, with five of six physical activity outcomes showing females were less active than males. Age had the most complex associations with self-report transport and leisure-time physical activity. Compared to older people, younger adults were less likely to engage in transport physical activity, but among those who did, younger people were likely to engage in more active minutes. Curvilinear associations were found between age and all three leisure-time physical activity outcomes, with the youngest and the oldest being more active. Positive associations with education were found for leisure-time physical activity only. There were significant interactions of city with sex and education for multiple physical activity outcomes.

Conclusions
Although socio-demographic correlates of physical activity are widely studied, the present results provide new information. City-specific findings suggest there will be value in conducting more detailed case studies. The curvilinear associations of age with leisure-time physical activity as well as significant interactions of leisure-time activity with sex and education should be further investigated. The findings of lower leisure-time physical activity among females as well as people with low education suggest that greater and continued efforts in physical activity policies and programs tailored to these high-risk groups are needed internationally.
Objectively measured physical activity in one-year-old children from a Brazilian cohort: levels, patterns and determinants
Authors: Ricardo Luiza Isnardi Cardoso , da Silva Inácio Crochemore M. , de Andrade Leão Otávio Amaral , Domingues Marlos Rodrigues , Wehrmeister Fernando C. 
Published: December 2019

Abstract
Background
The aim of this study is to describe objectively measured physical activity (PA) and its correlates in one-year-old children.

Methods
The current study includes participants from the 2015 Pelotas (Brazil) birth cohort. At age one, PA was assessed in a 24-h protocol during 4 days with a wrist-attached accelerometer (ActiGraph, wGT3X-BT), from which two complete days of data were analyzed, with 5-s epochs.

Results
A total of 2974 individuals provided valid accelerometry data. Infants able to walk independently spent on average 19 h per day below 50 mg of acceleration (including sleep time), and those who could not walk spent on average 21 h in this intensity category. Girls spent approximately 10 min more than boys below 50 mg daily in both walking status categories, and less activity than boys on higher intensity categories. Boys and infants whose mothers were more physically active during pregnancy presented more acceleration, regardless of walking status. Among infants who could walk by themselves, those with mothers with one to eight schooling years; adequate length-for-age (z-score); not attending daycare; and more physically active fathers also showed higher levels of acceleration.

Conclusions
Our findings demonstrate higher levels of PA among boys and those children with higher maternal PA during pregnancy, regardless of walking status. Also, among infants able to independently walk, 1–8 years of maternal schooling, adequate length-for-age (z-score), no daycare attendance and higher paternal PA are positive correlates of objectively measured PA early in life.
Elevated MR-proANP plasma concentrations are associated with sepsis and predict mortality in critically ill patients
Authors: Yagmur Eray , Sckaer Johanna Hermine , Koek Ger H. , Weiskirchen Ralf , Trautwein Christian , Koch Alexander , Tacke Frank 
Published: December 2019

AbstractBackground and aimsMid-regional pro atrial natriuretic peptide (MR-proANP) is an established biomarker for heart failure, based on its key role in regulating homeostasis of water balance and blood pressure. The aim of the study was to determine the value of MR-proANP as a clinical biomarker in critical illness and/or sepsis. Upon admission to the medical intensive care unit (ICU), we investigated MR-proANP plasma concentrations in 217 critically ill patients (144 with sepsis, 73 without sepsis). Results were compared with 65 healthy controls.ResultsMR-proANP plasma levels were significantly elevated in critically ill patients, when compared to healthy controls. Notably, MR-proANP levels were significantly higher in ICU patients with sepsis. MR-proANP levels were not associated with metabolic comorbidities like diabetes or obesity. In critically ill patients, MR-proANP plasma concentrations correlated with inflammatory cytokines, markers of organ dysfunction and several adipocytokines, such as resistin, retinol-binding protein 4 (RBP4) and adiponectin. Importantly, high MR-proANP plasma levels were associated with mortality, as MR-proANP levels above 227.0 pmol/l indicated a particularly increased mortality risk in ICU patients. The association between MR-proANP and mortality was independent of single organ failure and inflammation markers.ConclusionOur study emphasizes the role of circulating MR-proANP as a biomarker in critically ill patients, in which high MR-proANP indicates organ dysfunction, sepsis and mortality risk. The association between high MR-proANP and inflammatory as well as adipose tissue-derived endocrine mediators warrants further pathophysiological investigations.
Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model
Authors: Wagner Johannes M. , Schmidt Sonja V. , Dadras Mehran , Huber Julika , Wallner Christoph , Dittfeld Stephanie , Becerikli Mustafa , Jaurich Henriette , Reinkemeier Felix , Drysch Marius , Lehnhardt Marcus , Behr Björn 
Published: December 2019

AbstractBackgroundDelayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-union revealed an elevated osteoclast activity, accompanied by upregulated levels of TGF-beta and RANKL. Interestingly, scaphoid non-union seemed to be well vascularized.MethodsIn the current study, we used a murine femur-defect model to study atrophic non unions over a time-course of 10 weeks. Different time points were chosen, to gather insights into the dynamic processes of non-union establishment.ResultsHistological analyses as well as western blots and qRT-PCR indicated enhanced osteoclast activity throughout the observation period, paralleled by elevated levels of TGF-beta, TNF-alpha, MMP9, MMP13 and RANKL, especially during the early phases of non-union establishment. Interestingly, elevated levels of these mediators decreased markedly over a period of 10 weeks, as inflammatory reaction during non-union establishment seemed to wear out. To our surprise, osteoblastogenesis seemed to be unaffected during early stages of non-union establishment.ConclusionTaken together, we gained first insights into the establishment process of atrophic non unions, in which inflammatory processes accompanied by highly elevated osteoclast activity seem to play a leading role.
CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson’s disease
Authors: Li Yuanyuan , Niu Mengyue , Zhao Aonan , Kang Wenyan , Chen Zhichun , Luo Ningdi , Zhou Liche , Zhu Xiongwei , Lu Liming , Liu Jun 
Published: December 2019

AbstractBackgroundThe mechanisms underlying the pathogenesis and progression of Parkinson’s disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration inA53Tmice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia.MethodsAfter establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 inA53Tmice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation.ResultsWe confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia ofA53Tmice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation.ConclusionsOur study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.
Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes
Authors: Afonso Philippe V. , Cassar Olivier , Gessain Antoine 
Published: December 2019

AbstractHuman T cell leukemia virus (HTLV-1) is an oncoretrovirus that infects at least 10 million people worldwide. HTLV-1 exhibits a remarkable genetic stability, however, viral strains have been classified in several genotypes and subgroups, which often mirror the geographic origin of the viral strain. The Cosmopolitan genotype HTLV-1a, can be subdivided into geographically related subgroups, e.g. Transcontinental (a-TC), Japanese (a-Jpn), West-African (a-WA), North-African (a-NA), and Senegalese (a-Sen). Within each subgroup, the genetic diversity is low. Genotype HTLV-1b is found in Central Africa; it is the major genotype in Gabon, Cameroon and Democratic Republic of Congo. While strains from the HTLV-1d genotype represent only a few percent of the strains present in Central African countries, genotypes -e, -f, and -g have been only reported sporadically in particular in Cameroon Gabon, and Central African Republic. HTLV-1c genotype, which is found exclusively in Australo-Melanesia, is the most divergent genotype. This reflects an ancient speciation, with a long period of isolation of the infected populations in the different islands of this region (Australia, Papua New Guinea, Solomon Islands and Vanuatu archipelago). Until now, no viral genotype or subgroup is associated with a specific HTLV-1-associated disease. HTLV-1 originates from a simian reservoir (STLV-1); it derives from interspecies zoonotic transmission from non-human primates to humans (ancient or recent). In this review, we describe the genetic diversity of HTLV-1, and analyze the molecular mechanisms that are at play in HTLV-1 evolution. Similar to other retroviruses, HTLV-1 evolves either through accumulation of point mutations or recombination. Molecular studies point to a fairly low evolution rate of HTLV-1 (between 5.6E−7 and 1.5E−6 substitutions/site/year), supposedly because the virus persists within the host via clonal expansion (instead of new infectious cycles that use reverse transcriptase).
Retraining walking over ground in a powered exoskeleton after spinal cord injury: a prospective cohort study to examine functional gains and neuroplasticity
Authors: Khan Atif S. , Livingstone Donna C. , Hurd Caitlin L. , Duchcherer Jennifer , Misiaszek John E. , Gorassini Monica A. , Manns Patricia J. , Yang Jaynie F. 
Published: December 2019

Abstract
Background
Powered exoskeletons provide a way to stand and walk for people with severe spinal cord injury. Here, we used the ReWalk exoskeleton to determine the training dosage required for walking proficiency, the sensory and motor changes in the nervous system with training, and the functionality of the device in a home-like environment.

Methods
Participants with chronic (> 1 yr) motor complete or incomplete spinal cord injury, who were primarily wheelchair users, were trained to walk in the ReWalk for 12 weeks. Measures were taken before, during, immediately after, and 2–3 months after training. Measures included walking progression, sitting balance, skin sensation, spasticity, and strength of the corticospinal tracts.

Results
Twelve participants were enrolled with 10 completing training. Training progression and walking ability: The progression in training indicated about 45 sessions to reach 80% of final performance in training. By the end of training, participants walked at speeds of 0.28–0.60 m/s, and distances of 0.74–1.97 km in 1 h. The effort of walking was about 3.3 times that for manual wheelchair propulsion. One non-walker with an incomplete injury became a walker without the ReWalk after training. Sensory and motor measures: Sitting balance was improved in some, as seen from the limits of stability and sway speed. Neuropathic pain showed no long term changes. Change in spasticity was mixed with suggestion of differences between those with high versus low spasticity prior to training. The strength of motor pathways from the brain to back extensor muscles remained unchanged. Adverse events: Minor adverse events were encountered by the participants and trainer (skin abrasions, non-injurious falls). Field testing: The majority of participants could walk on uneven surfaces outdoors. Some limitations were encountered in home-like environments.

Conclusion
For individuals with severe SCI, walking proficiency in the ReWalk requires about 45 sessions of training. The training was accompanied by functional improvements in some, especially in people with incomplete injuries.

Trial registration
NCT02322125 Registered 22 December 2014.
In-depth analysis of the replication cycle of Orpheovirus
Authors: Souza Fernanda , Rodrigues Rodrigo , Reis Erik , Lima Maurício , La Scola Bernard , Abrahão Jônatas 
Published: December 2019

AbstractBackgroundAfter the isolation of Acanthamoeba polyphaga mimivirus (APMV), the study and search for new giant viruses has been intensified. Most giant viruses are associated with free-living amoebae of the genusAcanthamoeba; however other giant viruses have been isolated inVermamoeba vermiformis, such as Faustovirus, Kaumoebavirus and Orpheovirus. These studies have considerably expanded our knowledge about the diversity, structure, genomics, and evolution of giant viruses. Until now, there has been only one Orpheovirus isolate, and many aspects of its life cycle remain to be elucidated.MethodsIn this study, we performed an in-depth characterization of the replication cycle and particles of Orpheovirus by transmission and scanning electron microscopy, optical microscopy and IF assays.ResultsWe observed, through optical and IF microscopy, morphological changes inV. vermiformiscells during Orpheovirus infection, as well as increased motility at 12 h post infection (h.p.i.). The viral factory formation and viral particle morphogenesis were analysed by transmission electron microscopy, revealing mitochondria and membrane recruitment into and around the electron-lucent viral factories. Membrane traffic inhibitor (Brefeldin A) negatively impacted particle morphogenesis. The first structure observed during particle morphogenesis was crescent-shaped bodies, which extend and are filled by the internal content until the formation of multi-layered mature particles. We also observed the formation of defective particles with different shapes and sizes. Virological assays revealed that viruses are released from the host by exocytosis at 12 h.p.i., which is associated with an increase of particle counts in the supernatant.ConclusionsThe results presented here contribute to a better understanding of the biology, structures and important steps in the replication cycle of Orpheovirus.