bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise training for lung transplant candidates and recipients: a systematic review
Authors: Hume Emily , Ward Lesley , Wilkinson Mick , Manifield James , Clark Stephen , Vogiatzis Ioannis
Published: October 2020

Exercise intolerance and impaired quality of life (QoL) are characteristic of lung transplant candidates and recipients. This review investigated the effects of exercise training on exercise capacity, QoL and clinical outcomes in pre- and post-operative lung transplant patients.

A systematic literature search of PubMed, Nursing and Allied Health, Cochrane (CENTRAL), Scopus and CINAHL databases was conducted from inception until February, 2020. The inclusion criteria were assessment of the impact of exercise training before or after lung transplantation on exercise capacity, QoL or clinical outcomes.

21 studies met the inclusion criteria, comprising 1488 lung transplant candidates and 1108 recipients. Studies consisted of five RCTs, two quasi-experimental and 14 single-arm cohort or pilot studies. Exercise training improved or at least maintained exercise capacity and QoL before and after lung transplantation. The impact on clinical outcomes was less clear but suggested a survival benefit. The quality of evidence ranged from fair to excellent.

Exercise training appears to be beneficial for patients before and after lung transplantation; however, the evidence for direct causation is limited by the lack of controlled trials. Well-designed RCTs are needed, as well as further research into the effect of exercise training on important post-transplant clinical outcomes, such as time to discharge, rejection, infection, survival and re-hospitalisation.
The effects of lung volume reduction treatment on diffusing capacity and gas exchange
Authors: van Dijk Marlies , Klooster Karin , Ten Hacken Nick H.T. , Sciurba Frank , Kerstjens Huib. A.M. , Slebos Dirk-Jan
Published: October 2020

Lung volume reduction (LVR) treatment in patients with severe emphysema has been shown to have a positive effect on hyperinflation, expiratory flow, exercise capacity and quality of life. However, the effects on diffusing capacity of the lungs and gas exchange are less clear.

In this review, the possible mechanisms by which LVR treatment can affect diffusing capacity of the lung for carbon monoxide (DLCO) and arterial gas parameters are discussed, the use ofDLCOin LVR treatment is evaluated and other diagnostic techniques reflecting diffusing capacity and regional ventilation (V′)/perfusion (Q′) mismatch are considered.

A systematic review of the literature was performed for studies reporting onDLCOand arterial blood gas parameters before and after LVR surgery or endoscopic LVR with endobronchial valves (EBV).DLCOafter these LVR treatments improved (40 studies, n=1855) and the mean absolute change from baseline in % predictedDLCOwas +5.7% (range −4.6% to +29%), with no real change in blood gas parameters. Improvement inV′ inhomogeneity andV′/Q′ mismatch are plausible explanations for the improvement inDLCOafter LVR treatment.
Alveolar proteinosis of genetic origins
Authors: Hadchouel Alice , Drummond David , Abou Taam Rola , Lebourgeois Muriel , Delacourt Christophe , de Blic Jacques
Published: October 2020

Pulmonary alveolar proteinosis (PAP) is a rare form of chronic interstitial lung disease, characterised by the intra-alveolar accumulation of lipoproteinaceous material. Numerous conditions can lead to its development. Whereas the autoimmune type is the main cause in adults, genetic defects account for a large part of cases in infants and children. Even if associated extra-respiratory signs may guide the clinician during diagnostic work-up, next-generation sequencing panels represent an efficient diagnostic tool. Exome sequencing also allowed the discovery of new variants and genes involved in PAP. The aim of this article is to summarise our current knowledge of genetic causes of PAP.
A New Method to Calculate Water Film Stiffness and Damping for Water Lubricated Bearing with Multiple Axial Grooves
Authors: Ren Guojun
Published: October 2020

Water lubricated guide bearings for hydro turbines and pumps are conventionally designed with multiple axial grooves to provide effectively cooling and flushing away abrasives. Due to the variety of groove configuration in terms of number and size, a predication of their performance is difficult. This paper deals with an analytical procedure to investigate groove effect on load capacity, stiffness and damping for this type of bearing where it is considered as an assembly of many inclined slide bearings. The result can be applied to bearings made of hard materials combined with low bearing pressure.
Public attitudes towards screening for kidney cancer: an online survey
Authors: Harvey-Kelly Laragh L. W. , Harrison Hannah , Rossi Sabrina H. , Griffin Simon J. , Stewart Grant D. , Usher-Smith Juliet A.
Published: October 2020

Background

Kidney cancer is often asymptomatic, leading to proposals for a screening programme. The views of the public towards introducing a new screening programme for kidney cancer are unknown. The aim of this study was to explore attitudes towards kidney cancer screening and factors influencing intention to attend a future screening programme.

Methods

We conducted an online population-based survey of 1021 adults aged 45–77 years. The main outcome measure was intention to attend four possible screening tests (urine, blood, ultrasound scan, low-dose CT) as well as extended low-dose CT scans within lung cancer screening programmes. We used multivariable regression to examine the association between intention and each screening test.

Results

Most participants stated that they would be ‘very likely’ or ‘likely’ to undergo each of the screening tests [urine test: n = 961 (94.1%); blood test: n = 922 (90.3%); ultrasound: n = 914 (89.5%); low-dose CT: n = 804 (78.8%); lung CT: n = 962 (95.2%)]. Greater intention to attend was associated with higher general cancer worry and less perceived burden/inconvenience about the screening tests. Less worry about the screening test was also associated with higher intention to attend, but only in those with low general cancer worry (cancer worry scale ≤ 5). Compared with intention to take up screening with a urine test, participants were half as likely to report that they intended to undergo blood [OR 0.56 (0.43–0.73)] or ultrasound [OR 0.50 (0.38–0.67)] testing, and half as likely again to report that they intended to take part in a screening programme featuring a low dose CT scan for kidney cancer screening alone [OR 0.19 (0.14–0.27)].

Conclusion

Participants in this study expressed high levels of intention to accept an invitation to screening for kidney cancer, both within a kidney cancer specific screening programme and in conjunction with lung cancer screening. The choice of screening test is likely to influence uptake. Together these findings support on-going research into kidney cancer screening tests and the potential for combining kidney cancer screening with existing or new screening programmes.
Use of digital periodontal data to compare periodontal treatment outcomes in a practice-based research network (PBRN): a proof of concept
Authors: Peikert Stefanie Anna , Mittelhamm Felix , Frisch Eberhard , Vach Kirstin , Ratka-Krüger Petra , Woelber Johan Peter
Published: October 2020

Background

Scientific studies in dentistry are mainly conducted at universities. However, most patients are treated in dental practices, which differ in many ways from treatment at the university. Through the establishment of practice-based research networks, however, it is also possible to examine studies in a real-world setting in dental practices. For this reason the aim of this non-interventional, observational study was to develop and evaluate a digital procedure to access, extract and analyse recorded clinical data in practices to assess periodontal treatment outcomes.

Methods

Participating periodontists were former or active postgraduate students of a master’s course in periodontics in Freiburg who routinely used a digital periodontal diagnostic program. All available stored periodontal patient charts were extracted, anonymized and digitally sent to the study centre.

Results

In this study, data were collected from 6301 patients from 9 different practices. Information such as probing depth (PD), bleeding on probing (BOP), mobility, furcation and gingival attachment for 153,163 teeth at first visit were successfully transferred to the study centre. During the average observational period of 9.77 years, only 2.8% of all teeth were lost. The number of visits was significantly negatively correlated with BOP (p < 0.0001), and the number of BOP-positive sites was significantly correlated with deeper PDs (p < 0.001).

Conclusion

The presented procedure was able to gather a large amount of practice-based periodontal data, and thus this study may support practice-based research networks. The data indicate that systematic and supportive periodontal therapy is successful on a practice-based level.

Trial registration The study was internationally registered on 4 January 2017 in the German Clinical Trials Register (DRKS 00011448). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011448
Cluster analysis of differences in medical economic burden among residents of different economic levels in Guangdong Province, China
Authors: Chen Jialong , Yang Liuna , Qian Zhenzhu , Sun Mingwei , Yu Honglin , Ma Xiaolei , Wan Chonghua , Yang Yunbin
Published: October 2020

Background

This study compares and analyzes the differences of residents’ medical economic burden in different economic levels, explores the factors for improving the equity of health services in Guangdong, China.

Methods

Cluster analysis was carried out in 20 cities of Guangdong Province by taking 7 key factors on the equity of health services as indicators. Seven key factors were collected from Guangdong Statistical Yearbook 2017 and the Sixth National Population Census. R-type clustering was used to reduce the dimensionality of 7 candidate variables through similarity index. Q-type clustering was used to classify 20 cities in Guangdong Province.

Results

The cluster analysis divided Guangdong Province into three regions with different medical economic burden. The greater the proportion of the elderly over 65 years old, the greater the proportion of health care expenditure to per capita consumer expenditure of residents, and the heavier the medical economic burden. On average, 10.75% of the general budget expenditure of each city in Guangdong Province is spent on health care.

Conclusions

The lower per capita GDP, the higher proportion of the elderly over 65 years old and the lack of medical technicians are risk factors for the heavier medical burden of the residents and the fairness of health services. While increasing the health expenditure, the government needs to further complete the reform of the medical and health system, improve the efficiency of the medical system and curb the rapid rise of absolute health expenditures of individuals, which can reduce the economic burden of residents’ medical care.
Genetic architecture of cardiometabolic risks in people living with HIV
Authors: Cheng Haoxiang , Sewda Anshuman , Marquez-Luna Carla , White Sierra R. , Whitney Bridget M. , Williams-Nguyen Jessica , Nance Robin M. , Lee Won Jun , Kitahata Mari M. , Saag Michael S. , Willig Amanda , Eron Joseph J. , Mathews W. Christopher , Hunt Peter W. , Moore Richard D. , Webel Allison , Mayer Kenneth H. , Delaney Joseph A. , Crane Paul K. , Crane Heidi M. , Hao Ke , Peter Inga
Published: October 2020

Background

Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown.

Methods

We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH.

Results

We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI.

Conclusions

Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.
Calcinosis in a roe deer fawn (Capreolus capreolus) in northern Germany
Authors: Wagener Matthias Gerhard , Lehmbecker Annika , Bühler Melanie , Wilkens Mirja , Punsmann Teresa , Ganter Martin
Published: October 2020

Background

Calcinosis has been reported for a broad range of different animals. Causes for calcinosis include metabolic disorders due to kidney failure, intoxication with calcinogenic plants, or iatrogenic overdose of vitamin D. Especially young animals seem to be very susceptible to developing calcinosis. Currently, however, there is a lack of information on calcinosis in wildlife.

Case presentation

The following case report describes a roe deer fawn admitted to a clinic due to general weakness and myiasis. Plasma levels for creatinine, urea and phosphate were highly elevated, whereas the total calcium level was decreased. Necropsy revealed calcinosis due to calcification in many organs. The reason for calcinosis in this particular case might be kidney failure. Plasma samples from other hunted roe deer fawns also showed high phosphate levels.

Conclusions

Roe deer fawns might be susceptible to calcinosis due to high plasma phosphate, which could be a result of kidney failure or different feed. Further research into calcium and phosphate homeostasis in roe deer is necessary.
Genetic variation in Japanese Holstein cattle for EBL development
Authors: Inagaki Yasuko , Kobayashi Tomoko , Suda Yoshihito , Kusama Kazuya , Imakawa Kazuhiko
Published: October 2020

Background

Infection with bovine leukemia virus (BLV), the causative agent for enzootic bovine leukosis (EBL), is increasing in dairy farms of Japan. The tendency of tumor development following BLV infection in certain cow families and bull lines has previously been described. We therefore hypothesized the existence of a genetic component which differentiates cattle susceptibility to the disease.

Results

We analyzed routinely collected large-scale data including postmortem inspection data, which were combined with pedigree information and epidemiological data of BLV infection. A total of 6,022 postmortem inspection records of Holstein cattle, raised on 226 farms served by a regional abattoir over 10 years from 2004 to 2015, were analyzed for associations between sire information and EBL development. We then identified statistically the relative susceptibility to EBL development for the progeny of specific sires and paternal grandsires (PGSs). The heritability of EBL development was calculated as 0.19. Similarly, proviral loads (PVLs) of progeny from identified sires and PGSs were analyzed, but no significant differences were found.

Conclusions

These observations suggest that because EBL development in our Holstein population is, at least in part, influenced by genetic factors independent of PVL levels, genetic improvement for lower incidence of EBL development in cattle notwithstanding BLV infection is possible.
Social capital, policy fairness, and subjective life satisfaction of earthquake survivors in Wenchuan, China: a longitudinal study based on post-earthquake survey data
Authors: Wang Dianxi , Li Danyang
Published: October 2020

Background

Existing research has rarely examined an earthquake’s sustained impact and the trajectory of the earthquake survivors’ life satisfaction over time. This study aims to analyze longitudinal changes in life satisfaction of Wenchuan earthquake survivors and the impact of social capital and government relief policy.

Methods

This research applied a hierarchical linear model to longitudinal survey data collected after the earthquake. The survey was divided into three waves and was collected from Deyang City and Mianyang City of Sichuan Province. A random sampling method was used; a sample of 225 participants had valid responses over three waves of the survey.

Results

This study found that a survivor’s social capital and the perception of the fairness of government relief policy have a significant effect on the trajectory of life satisfaction post-disaster. First, the initial life satisfaction of those with high social capital was significantly higher than of those with low social capital, whilst survivors with high social capital had a lower rate of change in life satisfaction. Second, one year after the earthquake, those who felt government policy was unfair had a lower life satisfaction than those who felt it was fair. However, from the first year to the fourth year after the disaster, survivors who believed that the government policy was unfair experienced a higher rate of change in life satisfaction than those who did not. Third, the fairness of government relief policy moderates the relationship between survivors’ social capital and changes in life satisfaction. A fair policy of relief can reduce the negative impact of the lack of individual social capital on life satisfaction.

Conclusions

Survivors reconstruct life satisfaction through their social network and the perception of the fairness of the government’s post-disaster relief policy. Therefore, to promote the improvement of life satisfaction of survivors, it is necessary to cultivate social capital and ensure fairness of the relief policy.
Switching of vascular cells towards atherogenesis, and other factors contributing to atherosclerosis: a systematic review
Authors: Shafi Ovais
Published: October 2020

Background

Onset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates the changes in vasculature that contribute to switching of vascular cells towards atherogenesis, focusing mainly on ageing.

Methods

Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving atherogenesis, vascular homeostasis, aging, gene expression, signaling pathways, angiogenesis, vascular development, vascular cell differentiation and maintenance, vascular stem cells, endothelial and vascular smooth muscle cells.

Results

Atherogenesis is a complex multistep process that unfolds in a sequence. It is caused by alterations in: epigenetics and genetics, signaling pathways, cell circuitry, genome stability, heterotypic interactions between multiple cell types and pathologic alterations in vascular microenvironment. Such alterations involve pathological changes in: Shh, Wnt, NOTCH signaling pathways, TGF beta, VEGF, FGF, IGF 1, HGF, AKT/PI3K/ mTOR pathways, EGF, FOXO, CREB, PTEN, several apoptotic pathways, ET – 1, NF-κB, TNF alpha, angiopoietin, EGFR, Bcl − 2, NGF, BDNF, neurotrophins, growth factors, several signaling proteins, MAPK, IFN, TFs, NOs, serum cholesterol, LDL, ephrin, its receptor pathway, HoxA5, Klf3, Klf4, BMPs, TGFs and others.

This disruption in vascular homeostasis at cellular, genetic and epigenetic level is involved in switching of the vascular cells towards atherogenesis. All these factors working in pathologic manner, contribute to the development and progression of atherosclerosis.

Conclusion

The development of atherosclerosis involves the switching of gene expression towards pro-atherogenic genes. This happens because of pathologic alterations in vascular homeostasis. When pathologic alterations in epigenetics, genetics, regulatory genes, microenvironment and vascular cell biology accumulate beyond a specific threshold, then the disease begins to express itself phenotypically. The process of biological ageing is one of the most significant factors in this aspect as it is also involved in the decline in homeostasis, maintenance and integrity.

The process of atherogenesis unfolds sequentially (step by step) in an interconnected loop of pathologic changes in vascular biology. Such changes are involved in ‘switching’ of vascular cells towards atherosclerosis.
Mitochondrial DNA drives noncanonical inflammation activation via cGAS–STING signaling pathway in retinal microvascular endothelial cells
Authors: Guo Yue , Gu Ruiping , Gan Dekang , Hu Fangyuan , Li Gang , Xu Gezhi
Published: October 2020

Background

Pathological stimuli cause mitochondrial damage and leakage of mitochondrial DNA (mtDNA) into the cytosol, as demonstrated in many cell types. The cytosolic mtDNA then drives the activation of noninfectious inflammation. Retinal microvascular endothelial cells (RMECs) play an important role in the inner endothelial blood–retinal barrier (BRB). RMEC dysfunction frequently occurs in posterior-segment eye diseases, causing loss of vision. In this study, we investigated the involvement of cytosolic mtDNA in noninfectious immune inflammation in RMECs under pathological stimuli.

Methods

RMECs were stimulated with 100 ng/ml lipopolysaccharide (LPS), 200 μM hydrogen peroxide (H2O2), or 25 mM d-glucose. After 24 h, immunofluorescent staining was used to detect the opening of the mitochondrial permeability transition pore (MPTP). Cytosolic mtDNA was detected with immunofluorescent staining and PCR after stimulation. mtDNA was then isolated and used to transfect RMECs in vitro, and the protein levels of cGAS were evaluated with western blotting. Real-time PCR was used to examine cGAS mRNA expression levels at different time points after mtDNA stimulation. The activation of STING was detected with immunofluorescent staining 6 h after mtDNA stimulation. Western blotting was used to determine the expression of STING and IFNβ, the phosphorylation status of TBK1, IRF3, and nuclear factor-κB (NF-κB) P65, and the nuclear translocation of IRF3 and NF-κB P65 at 0, 3, 6, 12, and 24 h. The mRNA expression of proinflammatory cytokines CCL4, CXCL10, and IFNB1, and transcription factor IRF1 were determined with real-time PCR, together with the concentrations of intercellular adhesion molecule 1 (ICAM-1) mRNA.

Results

Pathological stimuli caused mtDNA to leak into the cytosol by opening the MPTP in RMECs after 24 h. Cytosolic mtDNA regulated the expression of cGAS and the distribution of STING in RMECs. It promoted ICAM-1, STING and IFNβ expression, TBK1, IRF3, and NF-κB phosphorylation and the nuclear translocation in RMECs at 12 and 24 h after its transfection. The mRNAs of proinflammatory cytokines CCL4, CXCL10, and IFNB1, and transcription factor IRF1 were significantly elevated at 12 and 24 h after mtDNA stimulation.

Conclusions

Pathological stimulation induces mtDNA escape into the cytosol of RMECs. This cytoplasmic mtDNA is recognized by the DNA sensor cGAS, increasing the expression of inflammatory cytokines through the STING–TBK1 signaling pathway.
Targeting connexin 43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling
Authors: Yu Hailong , Cao Xiang , Li Wei , Liu Pinyi , Zhao Yuanyuan , Song Lilong , Chen Jian , Chen Beilei , Yu Wenkui , Xu Yun
Published: October 2020

Background

In the central nervous system (CNS), connexin 43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Similar to Cx43 overexpression, abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies. However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear.

Methods

Hemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH models in vitro and in vivo. After ICH injury, the Cx43 mimetic peptide Gap19 was used for treatment. Ethidium bromide (EtBr) uptake assays were used to measure the opening of Cx43Hcs. Western blotting and immunofluorescence were used to measure protein expression. qRT-PCR and ELISA were used to determine the levels of cytokines. Coimmunoprecipitation (Co-IP) and the Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins.

Results

In this study, Cx43 expression upregulation and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19 significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition, Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture. However, Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased Yes-associated protein (YAP) nuclear translocation. This subsequently upregulated SOCS1 and SOCS3 expression and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor, verteporfin (VP), reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury.

Conclusions

This study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs. Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 has anti-inflammatory and neuroprotective effects after ICH injury.
Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3
Authors: Zhang Koudong , Hu Hang , Xu Juan , Qiu Limin , Chen Haitao , Jiang Xingzhi , Jiang Yongqian
Published: October 2020

Background

Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear.

Methods

The expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay.

Results

Circ_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells.

Conclusion

Circ_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.
Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection
Authors: Caruffo Mario , Mandakovic Dinka , Mejías Madelaine , Chávez-Báez Ignacio , Salgado Pablo , Ortiz Daniela , Montt Liliana , Pérez-Valenzuela Javiera , Vera-Tamargo Francisca , Yánez José Manuel , Wacyk Jurij , Pulgar Rodrigo
Published: October 2020

Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens.
Assessment of serum macrophage migration inhibitory factor (MIF), adiponectin, and other adipokines as potential markers of proteinuria and renal dysfunction in lupus nephritis: a cross-sectional study
Authors: Gamez-Nava Jorge Ivan , Diaz-Rizo Valeria , Perez-Guerrero Edsaul Emilio , Muñoz-Valle Jose Francisco , Saldaña-Cruz Ana Miriam , Fajardo-Robledo Nicte Selene , Jacobo-Cuevas Heriberto , Nava-Valdivia Cesar Arturo , Alcaraz-Lopez Miriam Fabiola , Trujillo Xochitl , Huerta Miguel , Cardona-Muñoz Ernesto German , Gonzalez-Lopez Laura
Published: October 2020

Background

To date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial.

Objective

To assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis.

Methods

Cross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (rs). Multivariable linear regression adjusted the variables associated with the severity of proteinuria.

Results

SLE patients had higher MIF (p = 0.02) and adiponectin (p < 0.001) than HCs. Patients with renal SLE involvement (n = 43) had higher adiponectin (19.0 vs 13.3 μg/mL,p = 0.002) and resistin (10.7 vs 8.9 ng/mL,p = 0.01) than patients with non-renal SLE (n = 153). Proteinuria correlated with high adiponectin (rs = 0.19,p < 0.009) and resistin (rs = 0.26,p < 0.001). MIF (rs = 0.27,p = 0.04). Resistin correlated with increased creatinine (rs = 0.18,p = 0.02). High renal-SLEDAI correlated with adiponectin (rs = 0.21,p = 0.004). Multiple linear regression showed that elevated adiponectin (p = 0.02), younger age (p = 0.04) and low MIF (p = 0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R2 = 0.41).

Conclusions

High adiponectin combined with low MIF concentrations int+eract to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.
Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury, with MASP-2 playing a major role
Authors: Mercurio D. , Oggioni M. , Fumagalli S. , Lynch N. J. , Roscher S. , Minuta D. , Perego C. , Ippati S. , Wallis R. , Schwaeble W. J. , De Simoni M.-G.
Published: October 2020

The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2−/−), ficolin-A (Fcna−/−), CL-11 (Colec11−/−), MASP-1/3 (Masp1−/−), MBL-C (Mbl2−/−), MBL-A (Mbl1−/−) or MBL−/− (Mbl1−/−/Mbl2−/−) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2−/−, MBL−/− and FCN-A−/− mice had better outcome scores compared to WT. Of these, MASP-2−/− mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2−/− mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI.
Wayfinding: How Ecological Perspectives of Navigating Dynamic Environments Can Enrich Our Understanding of the Learner and the Learning Process in Sport
Authors: Woods Carl T. , Rudd James , Robertson Sam , Davids Keith
Published: October 2020

Wayfinding is the process of embarking upon a purposeful, intentional, and self-regulated journey that takes an individual from an intended region in one landscape to another. This process is facilitated through an individual’s capacity to utilise temporally structured, functional actions embedded within a particular environmental niche. Thus, individuals learn of their performance landscapes by experiencing them through interactions, detecting and exploiting its many features to ‘find their way’. In this opinion piece, we argue that these ecological and anthropological conceptualisations of human navigation can, metaphorically, deepen our understanding of the learner and the learning process in sport, viewed through the lens of ecological dynamics. Specifically, we consider sports practitioners as (learning) landscape designers, and learners as wayfinders; individuals who learn to skilfully self-regulate through uncharted fields (composed of emergent problems) within performance landscapes through a deeply embodied and embedded perception-action coupling. We contend that, through this re-configuration of the learner and the learning process in sport, practitioners may better enact learning designs that afford learners exploratory freedoms, learning to perceive and utilise available opportunities for action to skilfully navigate through emergent performance-related problems. We conclude the paper by offering two practical examples in which practitioners have designed practice landscapes that situate learners as wayfinders and the learning process in sport as wayfinding.
‘Knowing as we go’: a Hunter-Gatherer Behavioural Model to Guide Innovation in Sport Science
Authors: Woods Carl T. , Robertson Sam , Rudd James , Araújo Duarte , Davids Keith
Published: October 2020

Where do novel and innovative ideas in sport science come from? How do researchers and practitioners collectively explore the dynamic landscape of inquiry, problem, solution and application? How do they learn to skilfully navigate from current place and practice toward the next idea located beyond their current vantage point? These questions are not just of philosophical value but are important for understanding how to provide high-quality support for athletes and sport participants at all levels of expertise and performance. Grounded in concepts from social anthropology, and theoretically positioned within an ecological dynamics framework, this opinion piece introduces a hunter-gatherer model of human behaviour based on wayfinding, situating it as a conceptual guide for implementing innovations in sport science. Here, we contend that the embedded knowledge of a landscape that guides a successful hunting and gathering party is germane to the pragmatic abduction needed to promote innovation in sport performance, leading to the inquisition of new questions and ways of resolving performance-preparation challenges. More specifically, exemplified through its transdisciplinarity, we propose that tohunt‘new ideas’ andgathertranslatable knowledge, sport science researchers and practitioners need to wayfind through uncharted regions located in new performance landscapes. It is through this process of navigation where individuals will deepen, enrich and grow current knowledge, ‘taking home’ new ideas as they find their way.
Rheumatic manifestations of COVID-19: a systematic review and meta-analysis
Authors: Ciaffi Jacopo , Meliconi Riccardo , Ruscitti Piero , Berardicurti Onorina , Giacomelli Roberto , Ursini Francesco
Published: October 2020

Background

Different proportions of musculoskeletal or autoimmune manifestations associated with COVID-19 have been reported in literature. We performed a systematic review and meta-analysis with the aim of assessing the prevalence of rheumatic manifestations in patients affected by COVID-19, as initial symptom or during disease course.

Methods

A database search was run on May 18th, 2020, using two distinct strategies. We were interested in the percentage of symptoms of potential rheumatologic interest observed in large population studies of COVID-19 cases, and in identifying uncommon autoimmune disorders described in patients with COVID-19. For manifestations individually reported, a meta-analysis was performed taking into consideration the proportion of COVID-19 patients presenting the symptom.

Results

Eighty eight original articles were included in the systematic review and 51 in the meta-analysis. We found pooled estimates of 19% for muscle pain and 32% for fatigue as initial symptom of COVID-19 presentation and, respectively, of 16 and 36% during the disease course. Only one article discussed arthralgia as unique symptom. Additionally, we found that vasculitis, chilblains, presence of autoantibodies commonly found in patients with rheumatic diseases, or autoimmune haematological and neurological disorders have all been reported in patients with COVID-19.

Conclusions

In conclusion, our review and meta-analysis emphasises that symptoms potentially leading to rheumatologic referral are common in patients with COVID-19. Therefore, COVID-19 is a new differential diagnosis to bear in mind when evaluating patients with musculoskeletal symptoms and rheumatologists might play a crucial role in identifying COVID-19 cases in early phases of the illness.
Modeling interconnected ICT and power systems for resilience analysis
Authors: Patil Amit Dilip , Haack Jonas , Braun Martin , Meer Hermann de
Published: October 2020

Increasing interdependencies between power and ICT systems amplify the possibility of cascading failures. Resilience against such failures is an essential property of modern and sustainable power systems and networks. To assess the resilience and predict the behaviour of a system consisting of interdependent subsystems, the interconnection requires adequate modeling. This work presents an approach to model and determine the state of these so-called interconnectors in future cyber-physical energy systems with strongly coupled ICT and power systems for a resilience analysis. The approach can be used to capture the impact of various parameters on system performance upon suitable modification. An hierarchical modeling approach is developed with atomic models that demonstrate the interdependencies between a power and ICT system. The modeling approach using stochastic activity nets is applied to an exemplary redispatch process in a cyber-physical energy system. The performance of an interconnector when facing limited performance from the ICT subsystem and its subsequent impact on the power system is analysed using the models. The state of the interconnector, as well as the service level are mapped to a resilience state-space diagram. The representation of system state on the resilience state-space diagram allows interpretation of system performance and quantification of resilience metrics.
Development and Impact of an Institutional Enhanced Recovery Program on Opioid Use, Length of Stay, and Hospital Costs Within an Academic Medical Center: A Cohort Analysis of 7774 Patients
Authors: Thiele Robert H. , Sarosiek Bethany M. , Modesitt Susan C. , McMurry Timothy L. , Tiouririne Mohamed , Martin Linda W. , Blank Randal S. , Shilling Ashley , Browne James A. , Bogdonoff David L. , Bauer Todd W. , Hedrick Traci L.
Published: October 2020

BACKGROUND:

Enhanced Recovery (ER) is a change management framework in which a multidisciplinary team of stakeholders utilizes evidence-based medicine to protocolize all aspects of a surgical care to allow more rapid return of function. While service-specific reports of ER adoption are common, institutional-wide adoption is complex, and reports of institution-wide ER adoption are lacking in the United States. We hypothesized that ER principles were generalizable across an institution and could be implemented across a multitude of surgical disciplines with improvements in length of stay, opioid consumption, and cost of care.

METHODS:

Following the establishment of a formal institutional ER program, ER was adopted in 9 distinct surgical subspecialties over 5 years at an academic medical center. We compared length of stay, opioid consumption, and total cost of care in all surgical subspecialties as a function of time using a segmented regression/interrupted time series statistical model.

RESULTS:

There were 7774 patients among 9 distinct surgical populations including 2155 patients in the pre-ER cohort and 5619 patients in the post-ER cohort. The introduction of an ER protocol was associated with several significant changes: a reduction in length of stay in 5 of 9 specialties; reduction in opioid consumption in 8 specialties; no change or reduction in maximum patient-reported pain scores; and reduction or no change in hospital costs in all specialties. The ER program was associated with an aggregate increase in profit over the study period.

CONCLUSIONS:

Institution-wide efforts to adopt ER can generate significant improvements in patient care, opioid consumption, hospital capacity, and profitability within a large academic medical center.
A Case Study of Stereoisomerism with [6]Cyclo[4]helicenylenes
Authors: Matsuno Taisuke , Yang Yong , Nanjo Yuki , Isobe Hiroyuki , Sato Sota
Published: October 2020

A noncylindrical cycloarylene was designed with [4]helicene as an arylene panel and was assembled by R/S-biaryl linkages. By determining the molecular structures of four stereoisomers (3 diastereomers and 1 enantiomer pair), we found that the structural mathematics of congeners can be best described by R/S-configurations of biaryls and not by panel orientations. Comparisons with structurally relevant cycloarylenes deepened our understanding of cyclostereoisomerism and structural chemistry.
The Importance of Commitment Power in Games with Imperfect Evidence
Authors: Silva Francisco
Published: October 2020

The literature initiated by Green and Laffont (1986) studies principal-agent models with hard evidence. Evidence is modeled by assuming that the message set of the agent is type dependent. In this setup, Glazer and Rubinstein (2004, 2006) and Sher (2011) show that when the agent’s utility function is type independent there is no advantage for the principal in having commitment power. This paper shows that this way of modeling evidence implicitly assumes it to be perfectly accurate and that the result that commitment power has no value is not robust to making the evidence imperfect. (JEL C70, D82)
Wzrost znaczenia instrumentów inwestycyjnych w polityce regionalnej Unii Europejskiej w perspektywie finansowej 2014-2020
Authors: Michalewska-Pawlak Małgorzata , Klimowicz Monika
Published: October 2020

The Increase of Significance Investment Instruments in Regional Policy of the European Union after 2014 The main objective of this paper is to analyse the increase of significance investment instruments in regional policy of the European Union after 2014. The reasons of this phenomenon have been pointed out in the context of the European Union structural funds. They refer to political interests, economic, social environmental challenges faced by the EU regions under conditions of limitation the EU expenditure on regional development financing. Solutions in the following areas: objectives, priorities and rules of intervention of the structural funds have been presented – those which have an investment dimension. Investment approach is going to be carried on in the next Multiannual Financial Framework after 2020. The paper has been elaborated based on using method of institutional analysis the key EU regional policy legal regulations and existing scientific literature.
Network-Based Approximate Linear Programming for Discrete Optimization
Authors: Nadarajah Selvaprabu , Cire Andre A.
Published: October 2020

Several prescriptive tasks in business and engineering as well as prediction in machine learning entail the solution of challenging discrete optimization problems. We recast the typical optimization formulation of these problems as high-dimensional dynamic programs and approach their approximation via linear programming. We develop tractable approximate linear programs with supporting theory by bringing together tools from state-space aggregations, networks, and perfect graphs (i.e., graph completions). We embed these models in a simple branch-and-bound scheme to solve applications in marketing analytics and the maintenance of energy or city-owned assets. We find that the resulting technique substantially outperforms a state-of-the-art commercial solver as well as aggregation-heuristics in terms of both solution quality and time. Our results motivate further consideration of networks and graph theory in approximate linear programming for solving deterministic and stochastic discrete optimization problems.