bluuebunny/crossref_metadata_2025 huggingface dataset:
Placentation and antitumor immunity regulated by a scaffolding protein in NK cells
Authors: Colucci Francesco
Published: August 2019

Natural killer cells use the Gab3 adaptor protein to limit trophoblast invasion during pregnancy and to reject tumor cells. See the related Research Article by

Sliz
et al

.
Sulfadiazine Sodium Ameliorates the Metabolomic Perturbation in Mice Infected with Toxoplasma gondii
Authors: Zhou Chun-Xue , Gan Yun , Elsheikha Hany M. , Chen Xiao-Qing , Cong Hua , Liu Qing , Zhu Xing-Quan
Published: August 2019

In this study, we analyzed the global metabolomic changes associated withToxoplasma gondiiinfection in mice in the presence or absence of sulfadiazine sodium (SDZ) treatment. BALB/c mice were infected withT. gondiiGT1 strain and treated orally with SDZ (250 μg/ml in water) for 12 consecutive days. Mice showed typical manifestations of illness at 20 days postinfection (dpi); by 30 dpi, 20% had survived and developed latent infection.
Emergence of Multidrug-Resistant Salmonella enterica Serovar Goldcoast Strains in Taiwan and International Spread of the ST358 Clone
Authors: Liao Ying-Shu , Chen Bo-Han , Hong Yu-Ping , Teng Ru-Hsiou , Wang You-Wun , Liang Shiu-Yun , Liu Yen-Yi , Tu Yueh-Hua , Chen Yi-Syong , Chang Jui-Hsien , Tsao Chi-Sen , Chiou Chien-Shun
Published: August 2019

Salmonella enterica
serovar Goldcoast infection was rare in Taiwan; it was not detected in routine surveillance from 2004 to 2013. This serovar was first identified in 2014, but the frequency of infection remained low until 2017. From 2014 to 2016, all but one isolate was pan-susceptible.
S
. Goldcoast infections abruptly increased in 2018, and all isolates were multidrug-resistant (MDR).
Lysogeny in the Lactic Acid Bacterium Oenococcus oeni Is Responsible for Modified Colony Morphology on Red Grape Juice Agar
Authors: Chaïb Amel , Philippe Cécile , Jaomanjaka Féty , Claisse Olivier , Jourdes Mickaël , Lucas Patrick , Cluzet Stéphanie , Le Marrec Claire
Published: August 2019

The presence of white and red colonies on red grape juice (RGJ) agar during enumeration ofOenococcus oeniin wine samples is frequently observed by stakeholders in the wine industry. Our study brings an explanation for this intriguing phenomenon and establishes a link between the white-red color switch and the lysogenic state ofO. oeni. It also provides a simple and inexpensive method to distinguish between lysogenic and nonlysogenic derivatives inO. oeniwith a minimum of expended time and effort. Noteworthy, the protocol could be adapted to two other species of LAB, namely,Leuconostoc citreumandLactobacillus plantarum. It could be an effective tool to provide genetic, ecological, and functional insights into lysogeny and aid in improving biotechnological processes involving members of the lactic acid bacterium (LAB) family.
How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery)
Authors: Pauwels Ans , Boecxstaens Veerle , Andrews Christopher N , Attwood Stephen E , Berrisford Richard , Bisschops Raf , Boeckxstaens Guy E , Bor Serhat , Bredenoord Albert J , Cicala Michele , Corsetti Maura , Fornari Fernando , Gyawali Chandra Prakash , Hatlebakk Jan , Johnson Scott B , Lerut Toni , Lundell Lars , Mattioli Sandro , Miwa Hiroto , Nafteux Philippe , Omari Taher , Pandolfino John , Penagini Roberto , Rice Thomas W , Roelandt Philip , Rommel Nathalie , Savarino Vincenzo , Sifrim Daniel , Suzuki Hidekazu , Tutuian Radu , Vanuytsel Tim , Vela Marcelo F , Watson David I , Zerbib Frank , Tack Jan
Published: August 2019

Objective

Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery.

Design

We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous.

Results

Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett’s oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis.

Conclusion

With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.
What constitutes a reasonable compensation for non-commercial oocyte donors: an analogy with living organ donation and medical research participation
Authors: Kool Emy , van der Graaf Rieke , Bos Annelies , Fauser Bartholomeus , Bredenoord Annelien
Published: August 2019

There is a growing consensus that the offer of a reasonable compensation for oocyte donation for reproductive treatment is acceptable if it does not compromise voluntary and altruistically motivated donation. However, how to translate this ‘reasonable compensation’ in practice remains unclear as compensation rates offered to oocyte donors between different European Union countries vary significantly. Clinics involved in oocyte donation, as well as those in other medical contexts, might be encouraged in calculating a more consistent and transparent compensation for donors if the elements that constitute a reasonable compensation are explicated. In doing so, lessons can be learnt from living organ donation and medical research participation. Practices in which the elements of a reasonable compensation for the individuals involved have already been more defined in the literature. By means of analogical reasoning, we will outline the different components of a reasonable compensation and subsequently apply these to the context of oocyte donation. We will argue that oocyte donors should first of all be reasonably reimbursed direct expenses related to the donation, without standard remuneration of lost wages. Second, donating oocytes requests a serious time investment, therefore donors are entitled to suitable compensation for their time spent and efforts made. Finally, we will explain that a reasonable compensation consisting of these two components allows for altruism to remain the key value of oocyte donation for reproductive treatment. However, if we acknowledge that donors’ motives are more complex and often include reasons from self-interest, the reasonable compensation may be complemented with modest (non)monetary benefits.
Unemployment and benefit claims by UK veterans in the new millennium: results from a record linkage study
Authors: Burdett Howard , Fear Nicola T , MacManus Deirdre , Wessely Simon , Rona Roberto J , Greenberg Neil
Published: August 2019

Objectives

In the first study of its kind in the UK, we linked pensions data on benefit claims with data from the King’s Military Cohort to assess uptake of unemployment and disability benefits in military veterans of the UK Armed Forces.

Methods

Benefits data were matched with data on the mental health, demographics and military-related variables for 7942 veterans who had previously served as regulars and transitioned to civilian life between 2003 and 2016. Associations between demographic and service-related factors and benefit claims were assessed using Cox regression to take into account period at risk.

Results

Around 20% of veterans claim unemployment benefits (UB) shortly after leaving, but this proportion drops rapidly to around 2% in the first 2 years post service. Receipt of disability benefits (DB) is less common (1.5%), but longer-term. The most consistent predictors of postservice benefit usage were: low rank (a proxy for socio-economic status while in service) (HR 1.42 (95% CI 1.23 to 1.65) for UB and 1.59 (95% CI 1.11 to 2.27) for DB); leaving service (HR 1.29 (95% CI 1.07 to 1.56) between unplanned leaving and UB, and 7.51 (95% CI 5.31 to 10.6) between medical discharge and DB), and having a history of claiming benefits before joining the Services (HR 1.62 (95% CI 1.34 to 1.95) between preservice and postservice UB, and 2.86 (95% CI 1.09 to 7.47) between preservice and postservice DB).

Conclusions

Benefit claims by veterans are largely driven by socioeconomic, rather than military, factors. Additional employment-focused support to Service leavers may be particularly useful to lower-ranked personnel and those leaving in an unplanned way. Continuity of care and medical oversight is a key concern for those with medical discharges.
Severity of chronic obstructive pulmonary disease with ‘exacerbator with emphysema phenotype’ is associated with potential biomarkers
Authors: Hao Wendong , Li Manxiang , Zhang Yunqing , Zhang Cailian , Wang Ping
Published: August 2019

Objective

The present study was designed to investigate the biomarkers levels of fractalkine (FKN), neutrophil elastase (NE) and matrix metalloproteinase-12 (MMP-12) in chronic obstructive pulmonary disease (COPD) with ‘exacerbator with emphysema phenotype’ and to evaluate the associations between the biomarkers levels and the severity of disease by spirometric measurements.

Methods

A total of 84 COPD patients and 49 healthy controls were enrolled in our study. ELISA were utilised to detect the FKN, MMP-12 and NE in serum from all subjects.

Results

FKN (p<0.001), NE (p=0.039) and MMP-12 (p<0.001) in serum of COPD patients showed higher levels than that of healthy control subjects. Serum FKN (p<0.001), MMP-12 (p<0.001) and NE (p=0.043) levels were significantly higher in severe and very severe COPD patients than that in mild and moderate COPD patients. Circulating FKN, MMP-12 and NE expression levels were significantly elevated (p<0.001) in COPD smokers compared with COPD non-smokers. The smoke pack years were negatively correlated with FEV1%pred (r=−0.5036), FEV1/FVC ratio (r=−0.2847) (FEV, forced expiratory volume; FVC, forced vital capacity). Similarly, we observed a strong positive correlation between the smoke pack years and serum levels of FKN (r=0.4971), MMP-12 (r=0.4315) and NE (r=0.2754). FEV1%pred was strongly negatively correlated with cytokine levels of FKN (r=−0.4367), MMP-12 (r=−0.3295) and NE (r=−0.2684). Likewise, FEV1/FVC ratio was negatively correlated with mediators of inflammation levels of FKN (r=−0.3867), MMP-12 (r=−0.2941) and NE (r=−0.2153).

Conclusion

Serum FKN, MMP-12 and NE concentrations in COPD patients are directly associated with the severity of COPD with ‘exacerbator with emphysema phenotype’. This finding suggests that FKN, MMP-12 and NE might play an important role in the pathophysiology of COPD.
Long-term safety and efficacy of sarilumab plus methotrexate on disease activity, physical function and radiographic progression: 5 years of sarilumab plus methotrexate treatment
Authors: Genovese Mark C , van der Heijde Désirée , Lin Yong , St John Gregory , Wang Sheldon , van Hoogstraten Hubert , Gómez-Reino Juan José , Kivitz Alan , Maldonado-Cocco José Antonio , Seriolo Bruno , Stanislav Marina , Burmester Gerd R
Published: August 2019

Objective

In MOBILITY (NCT01061736), sarilumab significantly reduced disease activity, improved physical function and inhibited radiographic progression at week 52 versus placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate. We report 5-year safety, efficacy and radiographic outcomes of sarilumab fromNCT01061736and the open-label extension (EXTEND;NCT01146652), in which patients received sarilumab 200 mg every 2 weeks (q2w) + methotrexate.

Methods

Patients (n=1197) with moderately to severely active RA were initially randomised to placebo, sarilumab 150 mg or sarilumab 200 mg subcutaneously q2w plus weekly methotrexate for 52 weeks. Completers were eligible to enrol in the open-label extension and receive sarilumab 200 mg q2w + methotrexate.

Results

Overall, 901 patients entered the open-label extension. The safety profile remained stable over 5-year follow-up and consistent with interleukin-6 receptor blockade. Absolute neutrophil count <1000 cells/mm3was observed but not associated with increased infection rate. Initial treatment with sarilumab 200 mg + methotrexate was associated with reduced radiographic progression over 5 years versus sarilumab 150 mg + methotrexate or placebo + methotrexate (mean±SE change from baseline in van der Heijde-modified Total Sharp Score: 1.46±0.27, 2.35±0.28 and 3.68±0.27, respectively (p<0.001 for each sarilumab dose versus placebo)). Clinical efficacy was sustained through 5 years according to Disease Activity Score (28-joint count) using C reactive protein, Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index. The number of patients achieving CDAI ≤2.8 at 5 years was similar among initial randomisation groups (placebo, 76/398 (19%); sarilumab 150 mg, 68/400 (17%); sarilumab 200 mg, 84/399 (21%)).

Conclusion

Clinical efficacy, including inhibition of radiographic progression, reduction in disease activity and improvement in physical function, was sustained with sarilumab + methotrexate over 5 years. Safety appeared stable over the 5-year period.
Cyclic Performance Evaluation of Hollow Structural Section (HSS) and Concrete-Filled Tube (CFT) Braces
Authors: Ebrahimi Samira , Zahrai Seyed Mehdi , Mirghaderi Seyed Rasoul
Published: August 2019

Hollow structural sections (HSS) are widely used as braces because they have inherent axial, flexural, and torsional capacities. Delaying or preventing local buckling is accomplished by concrete infill in HSS braces to improve their cyclic response heavily relying upon three key parameters: (1) presence of concrete infill, (2) width (diameter)-to-thickness ratio, and (3) length-to-width (diameter) ratio impress the cyclic response of HSS braces. Nevertheless, it is not clear that based on which parameter, concrete infill can significantly enhance the peak compressive strength and energy dissipation capacity of HSS braces. This paper aims to investigate this concern while presenting a numerical study on the cyclic response of 120 HSS and Concrete-Filled Tubes (CFT) braces with various geometric characteristics. Square and circular cross-sections, 10, 12, 13.33, 20, 30, 33.33, and 50 width (diameter)-to-thickness ratios and 10, 15, 20, 25, 30, 37.5, 45, 50, 75, and 112.5 length-to-width (diameter) ratios are selected for the numerical investigation. Obtained results indicated that concrete infill can increase peak compressive and post-buckling strengths and energy dissipation capacity of HSS braces around 81%, 43%, and 73%, respectively. It was found that concrete infill and parameters of width (diameter)-to-thickness ratio and length-to-width (diameter) ratio influence the cyclic response of HSS braces differently. On the other hand, concrete infill noticeably enhances the peak compressive strength of HSS braces with larger values of width (diameter)-to-thickness ratio and energy dissipation capacity of such braces with lower values of length-to-width (diameter) ratio.
A Novel Method to Search for the Wheel–Rail Contact Point
Authors: Liu Hanyun , Yu Zhiwu , Guo Wei , Jiang Lizhong , Kang Chongjie
Published: August 2019

This paper proposed the normal contact searching method (NCSM), a novel method to search for the wheel–rail contact point, which utilizes the normal maximum penetration distance between wheel and rail as the judgment condition. The contact point found by the NCSM can better represent the center of the wheel–rail contact patch which is considered more reasonable than the commonly used vertical contact searching method (VCSM), the latter adopts the vertical minimum distance to determine the wheel–rail contact point. The differences between these two methods are analyzed and compared for the same contact point situation and with same motion parameters. The results show that, for the Chinese LMA wheelset and CHN60 rail profiles, these two methods have slight differences for the same contact point situation. For a wheelset with a lateral displacement less than 7.0[Formula: see text]mm and with no yawing, the NCSM’s contact point is very close to VCSM’s, so both methods are suitable for the dynamic calculation. For a wheelset with a lateral displacement greater than 7.0[Formula: see text]mm or with yawing, an unreasonable jump occurs at the wheel–rail contact point and wheelset angle root contact by applying VCSM, while the NCSM has only small discrete jump on the wheelset tread contact. In this case, the NCSM instead of VCSM should be used in the dynamic analysis.
An extension of properties of symmetric group to monoids and a pretorsion theory in a category of mappings
Authors: Facchini Alberto , Heidari Zadeh Leila
Published: August 2019

Several elementary properties of the symmetric group [Formula: see text] extend in a nice way to the full transformation monoid [Formula: see text] of all maps of the set [Formula: see text] into itself. The group [Formula: see text] turns out to be the torsion part of the monoid [Formula: see text]. That is, there is a pretorsion theory in the category of all maps [Formula: see text], [Formula: see text] an arbitrary finite set, in which bijections are exactly the torsion objects.
Tangential Force Model for the Combined Finite-Discrete Element Method
Authors: Liu Xunnan , Zhao Lanhao , Mao Jia , Li Tongchun
Published: August 2019

In the past, contact model in the combined finite-discrete element method (FDEM) does not include the influence of the tangential contact interaction, and the deficient model associated with the contact force can seriously degrade the computing accuracy. In order to overcome this defect, an improved FDEM is developed in this work. The potential contact mechanism is implemented to calculate the normal contact force; meanwhile, the force-displacement law by coupling the classical Mohr–Coulomb type frictional algorithm and the rotation transformation algorithm is applied for the accurate computation of the tangential contact force. Consequently, a holonomic system of the calculation algorithm for the contact interaction is proposed, accounting for the influence of the tangential contact force. The performance of the approach is validated with well-known benchmarks including a frictional numerical test, the dynamic response of the block under the seismic excitation, a sliding/toppling test of a joint rock slope, a numerical simulation for joints structure affecting a sliding rock mass and the 2008 Donghekou Landslide trigged by the Wenchuan Earthquake. The results are compared against the experimental data and analytical solutions. Excellent agreements between the computational result and existing measurements show that the proposed approach has an outstanding ability to describe the complex mechanical properties among the separate entities.
THE ROLES OF ACADEMIC INVENTORS IN MEDICAL INNOVATION PROCESSES: EXPLORING THE INFLUENCE OF IPR OWNERSHIP AND IP NATURE
Authors: BRANTNELL ANDERS , BARALDI ENRICO
Published: August 2019

This paper analyses four medical innovation processes originating from Stanford and Uppsala universities with the purpose of understanding how intellectual property rights (IPR) ownership and intellectual property (IP) nature influence the behaviour of academic inventors. We analyse this behaviour through the roles enacted and evaluate the requirements the roles pose by developing a method to assess the requirements of individual roles, which we label as role intensity. We find that both IPR ownership and IP nature can influence the academic inventors’ roles and role intensities. In contrast to assumptions in research and policy, we find that IPR ownership does not influence the roles and role intensities in a remarkable way. We also find support that research and policy should distinguish between patentable and non-patentable inventions in the field of medical invention as these two types of IP nature are associated with different roles and role intensities. These findings contribute to the literature on commercialisation of science and innovation management by demonstrating the importance of IP nature in influencing the roles of inventors. Managerial and policy implications are provided.
Perturbations of urea cycle enzymes during posthepatectomy rat liver failure
Authors: Meier Michelle , Knudsen Anders Riegels , Andersen Kasper Jarlhelt , Ludvigsen Maja , Eriksen Peter Lykke , Pedersen Anne Kathrine Nissen , Honoré Bent , Mortensen Frank Viborg
Published: August 2019

Posthepatectomy liver failure (PHLF) may occur after extended partial hepatectomy (PH). If malignancy is widespread in the liver, the size of PH and hence the size of the future liver remnant (FLR) may limit curability. We aimed to characterize differences in protein expression between different sizes of FLRs and identify proteins specific to the regenerative process of minimal-size FLR (MSFLR), with special focus on postoperative day (POD) 1 when PHLF is present. A total of 104 male Wistar rats were subjected to 30, 70, or 90% PH (MSFLR in rats), sham operation, or no operation. Blood and liver tissue were harvested at POD1, 3, and 5 ( n = 8 per group). Protein expression was assessed by proteomic profiling by unsupervised two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) liquid chromatography tandem mass spectrometry (LC-MS/MS), followed by supervised selected reaction monitoring (SRM)-MS/MS. In all, 1,035 protein spots were detected, 54 of which were significantly differentially expressed between groups and identifiable. During PHLF after PH(90%) at POD1, urea cycle and related proteins showed significant perturbations, including the urea cycle flux-regulating enzyme of carbamoyl phosphate synthase-1, ornithine transcarbamylase, and arginase-1, as well as the ornithine aminotransferase and propionyl-CoA carboxylase alpha chain. Plasma-ammonia increased significantly at POD1 after PH(90%), followed by a prompt decrease. At the protein level, we found perturbations of urea cycle and related enzymes in the MSFLR during PHLF. Our results suggest that these perturbations may augment urea cycle function, which may be pivotal for increased ammonia elimination after extensive PHs and potential PHLF.

NEW & NOTEWORTHY Posthepatectomy liver failure (PHLF) is associated with high mortality. In a rat model of 90% hepatectomy, PHLF is present. Our results on liver tissue proteomics suggest that the ability of the liver remnant to sufficiently eliminate ammonia may be brought about by perturbation related to urea cycle proteins and that enhancing the urea cycle capacity may play a key role in surviving PHLF.
Dilated cardiomyopathy mutation (R174W) in troponin T attenuates the length-mediated increase in cross-bridge recruitment and myofilament Ca2+ sensitivity
Authors: Reda Sherif M. , Chandra Murali
Published: August 2019

Alterations in length-dependent activation (LDA) may constitute a mechanism by which cardiomyopathy mutations lead to deleterious phenotypes and compromised heart function, because LDA underlies the molecular basis by which the heart tunes myocardial force production on a beat-to-beat basis (Frank-Starling mechanism). In this study, we investigated the effect of DCM-linked mutation (R173W) in human cardiac troponin T (TnT) on myofilament LDA. R173W mutation is associated with left ventricular dilatation and systolic dysfunction and is found in multiple families. R173W mutation is in the central region (residues 80–180) of TnT, which is known to be important for myofilament cooperativity and cross-bridge (XB) recruitment. Steady-state and dynamic contractile parameters were measured in detergent-skinned guinea pig left ventricular muscle fibers reconstituted with recombinant guinea pig wild-type TnT (TnTWT) or mutant TnT (TnTR174W; guinea pig analog of human R173W mutation) at two different sarcomere lengths (SL): short (1.9 µm) and long (2.3 µm). TnTR174W decreased pCa50 (−log [Ca2+]free required for half-maximal activation) to a greater extent at long than at short SL; for example, pCa50 decreased by 0.12 pCa units at long SL and by 0.06 pCa units at short SL. Differential changes in pCa50 at short and long SL attenuated the SL-dependent increase in myofilament Ca2+ sensitivity (ΔpCa50) in TnTR174W fibers; ΔpCa50 was 0.10 units in TnTWT fibers but only 0.04 units in TnTR174W fibers. Furthermore, TnTR174W blunted the SL-dependent increase in the magnitude of XB recruitment. Our observations suggest that the R173W mutation in human cardiac TnT may impair Frank-Starling mechanism.

NEW & NOTEWORTHY This work characterizes the effect of dilated cardiomyopathy mutation in cardiac troponin T (TnTR174W) on myofilament length-dependent activation. TnTR174W attenuates the length-dependent increase in cross-bridge recruitment and myofilament Ca2+ sensitivity.
Adverse early-life environment impairs postnatal lung development in mice
Authors: Lai Pui Y. , Jing Xigang , Michalkiewicz Teresa , Entringer Brianna , Ke Xingrao , Majnik Amber , Kriegel Alison J. , Liu Pengyuan , Lane Robert H. , Konduri Girija G.
Published: August 2019

Background: Fetal growth restriction (FGR) is a major risk factor for bronchopulmonary dysplasia (BPD). Maternal stress and poor diet are linked to FGR. Effect of perinatal stress on lung development remains unknown. Objective: Using a murine model of adverse early life environment (AELE), we hypothesized that maternal exposure to perinatal environmental stress and high-fat diet (Western diet) lead to impaired lung development in the offspring. Methods: Female mice were placed on either control diet or Western diet before conception. Those exposed to Western diet were also exposed to perinatal environmental stress, the combination referred to as AELE. Pups were either euthanized at postnatal day 21 (P21) or weaned to control diet and environment until adulthood (8–14 wk old). Lungs were harvested for histology, gene expression by quantitative RT-PCR, microRNA profiling, and immunoblotting. Results: AELE increased the mean linear intercept and decreased the radial alveolar count and secondary septation in P21 and adult mice. Capillary count was also decreased in P21 and adult mice. AELE lungs had decreased vascular endothelial growth factor A (VEGFA), VEGF receptor 2, endothelial nitric oxide synthase, and hypoxia inducible factor-1α protein levels and increased expression of genes that regulate DNA methylation and upregulation of microRNAs that target genes involved in lung development at P21. Conclusion: AELE leads to impaired lung alveolar and vascular growth, which persists into adult age despite normalizing the diet and environment at P21. AELE also alters the expression of genes involved in lung remodeling.
Association of Epigenetic Clock with Consensus Molecular Subtypes and Overall Survival of Colorectal Cancer
Authors: Zheng Chunlei , Li Li , Xu Rong
Published: August 2019

Background:

Epigenetic clock, or DNA methylation age, has been shown to highly correlate with chronologic age. Epigenetic age acceleration, the difference between DNA methylation age and individual's chronologic age, was observed in colorectal cancer. However, the association of epigenetic age acceleration with colorectal cancer tumor molecular characteristics, clinical characteristics, and patient outcomes has not been systematically investigated.

Methods:

DNA methylation ages of 345 patients with colorectal cancer from The Cancer Genome Atlas (TCGA) were computed using the Horvath age prediction model. Multivariate linear regression was used to assess the association of epigenetic age acceleration with molecular and clinical features of colorectal cancer, including consensus molecular subtypes (CMS1–CMS4) and tumor stage Cox proportional hazards regression was used to assess the association of epigenetic age acceleration with survival.

Results:

Epigenetic age acceleration is significantly associated with CMS. Compared with CMS2, epigenetic age acceleration for CMS1, CMS3, and CMS4 was 23.90 years [P = 5.55E-11; 95% confidence interval (CI): 17.10–30.69], 9.16 years (P = 5.84E-03; 95% CI: 2.68–15.65), and 6.05 years (P = 2.69E-02; 95% CI: 0.70–11.41), respectively. Furthermore, epigenetic age acceleration is statistically significantly and positively associated with total mortality (HR = 1.97; 95% CI: 1.14–3.39; P = 0.014).

Conclusions:

Epigenetic age acceleration is associated with colorectal cancer tumor molecular characteristics, and a significant predictor of overall survival of colorectal cancer, along with age and tumor stage.

Impact:

Combining information of colonic tissue epigenetic age acceleration and tumor molecular characteristics may improve prognosis prediction in colorectal cancer.
O TERMO “LINGUAGEM” EM MOUNIN E SEUS PROBLEMAS TEÓRICOS DA TRADUÇÃO
Authors: Celli Marion
Published: August 2019

Este trabalho visa a descrever as impressões iniciais de uma pesquisa de doutorado em andamento cujo objetivo principal é estudar o conceito do termo “linguagem” em textos clássicos sobre tradução, a fim de contribuir para uma perspectiva da atividade de linguagem como alicerce do ato de traduzir (CULIOLI, 1990). O presente artigo tem como foco chamar a atenção para a explicitação conceitual do termo e apresentar o estudo de caso de um dos textos que compõem o corpus de estudo da pesquisa – a clássica obra Les problèmes théoriques de la traduction, do pensador francês Georges Mounin (1963). Tal discussão foi inspirada em nossa participação no X Encontro do Francês, evento anual do Programa de Pós-graduação em Estudos Linguísticos, Literários e Tradutológicos em Francês da Universidade de São Paulo.
Cambarus fetzneri sp. nov., a new species of burrowing crayfish (Decapoda: Cambaridae) from the Allegheny Mountains of Virginia and West Virginia, USA
Authors: LOUGHMAN ZACHARY J. , WELSH STUART A. , THOMA ROGER F.
Published: August 2019

The disjunct distribution of Cambarus monongalensis has led to speculation about its taxonomic status. An Appalachian Plateau population occurs in northern and central West Virginia and Southwestern Pennsylvania, and a mountain population occurs in the Allegheny Mountains and Ridge and Valley physiographic provinces of the Virginias. Herein we describe the mountain population as Cambarus fetzneri sp. nov. The two species differ genetically and morphologically, and have different color patterns. Specifically, C. fetzneri sp. nov. chelae lack extensive red coloration on the distal end of the propodus and dactyl, possess rostral margins that lack any red coloration, compared to C. monongalensis, which has extensive red coloration on the dactyl and propodus, as well as red rostral margins. Morphologically, the rostrum of C. fetzneri sp. nov. is shorter and wider than that of C. monongalensis. Also, adult C. fetzneri sp. nov. are considerably smaller in body size than those of C. monongalensis.
Intermittent Phosphate Usage for Pediatric Diabetic Ketoacidosis in the Setting of a Phosphate Shortage
Authors: Campbell Christopher T. , Gattoline Sarah , Kelly Brian
Published: August 2019

Purpose: Hypophosphatemia during pediatric diabetic ketoacidosis (DKA) is often replaced through a continuous infusion of intravenous (IV) fluids with potassium phosphate. In 2012, during an IV potassium phosphate shortage, providers were directed to oral replacement strategies to restrict IV products to those patients with severe hypophosphatemia. Intermittent oral and IV as needed doses for low phosphate levels replaced continuous administration in pediatric DKA. The purpose of this quality-improvement project was to determine whether the implemented IV phosphate restrictions resulted in less IV phosphate usage with no change in clinically relevant outcomes. Methods: In a retrospective chart analysis, pediatric patients less than 18 years of age admitted with a DKA diagnosis from June 2011 to December 2016 were divided into 2 groups: continuous and intermittent phosphate administration. Patients were excluded if they received both therapies. The primary outcome was the difference in IV phosphate administered. Secondary outcomes included the following: total phosphate received, the number of patients requiring as needed doses, phosphate levels at admission and discharge from pediatric intensive care unit (PICU), hospital length of stay, and PICU length of stay. Results: Phosphate restrictions resulted in a significantly lower usage of IV phosphate products in the intermittent group versus the continuous group (38.5 vs. 0 mmol, P < .0001). While total phosphate replacement was similar, intermittent phosphate administration was also associated with significantly lower minimum and discharge phosphate levels. Conclusions: During a phosphate salt shortage, restriction of continuous phosphate replacement in pediatric DKA management can reduce the amount of IV phosphate products used without any clinically meaningful change in outcomes.
The SUP-ICU Trial: Does It Confirm or Condemn the Practice of Stress Ulcer Prophylaxis?
Authors: Barletta Jeffrey F. , Buckley Mitchell S. , MacLaren Robert
Published: August 2019

Purpose: Stress ulcer prophylaxis (SUP) is routinely administered to critically ill patients for the prevention of stress ulcer–induced, clinically important bleeding (CIB). Recently, the value of SUP has been questioned due to the perceived decline in CIB and the potential for infectious complications secondary to acid suppressive therapy. The SUP-ICU trial is a large, randomized controlled trial comparing intravenous pantoprazole with placebo for the indication of SUP. It is hoped that this trial would answer many of the questions pertaining to the overall value of SUP. This article will provide an in-depth assessment of the SUP-ICU trial in the context of the overall body of literature in this area. Furthermore, applications for clinical practice and recommendations on the provision of SUP are provided. Summary: The SUP-ICU trial revealed no difference in the primary outcome of 90-day mortality with pantoprazole but lower rates of CIB were noted (which was a secondary outcome). Overall, these data provide important insight into the value of SUP along with other questions related to the provision of SUP such as the relationship between CIB and mortality, infectious complications, and enteral nutrition. Conclusions: The SUP-ICU trial is a landmark trial describing the value of SUP in a modern-day setting of intensive care unit (ICU) practice. The provision of SUP should be continued in high-risk patients. Future studies are ongoing that will add further insight to this routine practice.
Chest wall metastasis in postoperative thyroid cancer: a case report
Authors: Fan Jing-Jing , Chen Qiang
Published: August 2019

Thyroid cancer is common in China. Thyroid adenocarcinoma metastases can be local or distal metastasis. Local metastasis presents as a hard and fixed lymph node in the neck, while distant metastases are found in the lung, skull, vertebrae, and pelvis. However, thyroid follicular carcinomas are mostly observed in hematogenous metastases. The thyroid adenocarcinoma and follicular carcinoma of the thyroid gland are often misdiagnosed. Here, we report the case of a 53-year-old female patient. More than 2 years after her initial diagnosis, her left chest wall was physically examined. The results revealed a progressive enlargement that had a hard quality, poor activity, unclear boundary, pressure pain, and percussion pain. Thyroid follicular cell carcinoma was subsequently diagnosed and treated surgically. The thyroid carcinoma had multiple bone metastases, and the thyroid follicular carcinoma had spread to the chest wall through the blood vessels. Thus, preoperative procedures and follow-up should be strengthened because early pathological thyroid follicular carcinoma and thyroid adenoma can easily be misdiagnosed. Pathologic consultation and follow-ups should be strengthened to prevent misdiagnosis.
Experimental evaluation of a morphing leading edge concept
Authors: Sodja Jurij , Martinez Marcias J , Simpson John C , De Breuker Roeland
Published: August 2019

This article presents an experimental evaluation of a morphing leading edge demonstrator by investigating its morphed shape, the level of induced strains in the airfoil skin, the actuation force, and the morphing mechanism’s capability to lock and transfer the applied loads. In addition, a finite element model of the demonstrator is assembled comprising an elastic morphing skin and a kinematic morphing mechanism. The obtained results are used to assess whether the demonstrator performs according to the design objectives, such as the target shape, the character of the morphing deformation and the morphing mechanism locking, applied during the design process. The comparison between experimental and numerical results yielded a good agreement in terms of observed morphed shape and pertaining strains. The average difference in morphed shape was less than 0.08% chord at the maximum actuator extension. The observed difference in the respective strains was less than 400 micro-strains. A significant difference, up to 70%, was observed in the actuation force, which was attributed to the modelling assumptions and to the force measurement technique employed in the experiment. Nevertheless, both results show good qualitative agreement showing similar trends.
Vitamin D Deficiency in Patients With Idiopathic and Traumatic Osteochondritis Dissecans of the Talus
Authors: Fraissler Lukas , Boelch Sebastian Philipp , Schäfer Thomas , Walcher Matthias , Arnholdt Jörg , Maier Gerrit , Jakob Franz , Rudert Maximilian , Horas Konstantin
Published: August 2019

Background:

Low vitamin D levels are common in patients with foot and ankle disorders. We have previously demonstrated that juveniles diagnosed with osteochondritis dissecans (OCD) have a high prevalence of vitamin D deficiency. Moreover, there is evidence that OCD might be related to vitamin D deficiency in general. However, whether or not hypovitaminosis D is associated with OCD of the talus has yet to be elucidated.

Methods:

The aim of this study was to determine serum vitamin D levels [25(OH)D] of patients diagnosed with traumatic and idiopathic OCD of the talus. The vitamin D status of patients was measured and correlated to age, sex, season, etiology, laterality, degree of disease, and nicotine abuse. Moreover, parathyroid hormone and serum calcium levels of patients were obtained to assess for severe vitamin D deficiency and secondary hyperparathyroidism. Between January 2015 and December 2017, 65 patients with a mean age of 38.9 years and a total of 68 lesions were identified.

Results:

In total, 75.4% of patients had low vitamin D levels with a mean overall 25(OH)D level of 24.2 ng/mL. Specifically, 35.4% of patients were vitamin D deficient; another 40% were vitamin D insufficient, and only 24.6% of patients presented with sufficient vitamin D levels. Statistical analysis showed no significant difference comparing vitamin D levels of patients with idiopathic OCD to patients with traumatic OCD.

Conclusion:

We could not find any significant differences in the vitamin D status of patients with OCD of the talus compared with patients with foot and ankle disorders in general. However, we found that vitamin D deficiency was frequent in patients presenting with traumatic and idiopathic OCD of the talus. We believe it might be beneficial to routinely assess and treat the vitamin D status of patients.

Level of Evidence:

Level III, retrospective comparative study.
Impact of environmental characteristics in urban green spaces on outdoor thermal environment: A case study of Wuhan City, China
Authors: Li Kun , Liu Xi , Zhou Jie
Published: August 2019

The design of urban spaces could greatly influence the ability of green spaces to improve the thermal environment. Wuhan in the hot-summer and cold-winter zone situated in the central and lower reaches of the Yangtze River in China, has numerous green parks and other natural resources. There is a demand to integrate environmental resources to improve the thermal environment in this city. This research was conducted using multidisciplinary methods including remote sensing inversion, extraction of spatial information, measurement of a multisystem thermal environment index, questionnaires, computational simulations and statistical analysis. By using these methods, the relationship was established between different types of green spaces, urban layouts in different scales and thermal environmental parameters. A multidimensional method for the design of green and urban spaces was developed with the aim to improve the urban thermal environment. The results showed that the relationship among thermal comfort parameters, such as temperature, wind speed and humidity would be influenced by urban layout surfaces and had close relationship with the characteristics of residents' behaviours. The regression models using the physiological equivalent temperature can express the condition of thermal comfort in green spaces quantitatively.
The impact of sex, age and training on biventricular cardiac adaptation in healthy adult and adolescent athletes: Cardiac magnetic resonance imaging study
Authors: Csecs Ibolya , Czimbalmos Csilla , Toth Attila , Dohy Zsofia , Suhai Imre F , Szabo Liliana , Kovacs Attila , Lakatos Balint , Sydo Nora , Kheirkhahan Mobin , Peritz David , Kiss Orsolya , Merkely Bela , Vago Hajnalka
Published: August 2019

Aims

Physiological cardiac adaptation in athletes is influenced by multiple factors. This study aimed to investigate the impact of sex, age, body size, sports type and training volume on cardiac adaptation in healthy athletes with cardiac magnetic resonance imaging.

Methods

A total of 327 athletes (242 male) were studied (adults ≥18 years old; adolescents 14–18 years old). Left and right ventricular ejection fractions, end-diastolic volume, end-systolic volume, stroke volumes and masses were measured. Left ventricular end-diastolic volume/left ventricular mass, right ventricular end-diastolic volume/right ventricular mass and derived right/left ventricular ratios were determined to study balanced ventricular adaptation. Athletes were categorised as skill, power, mixed and endurance athletes.

Results

Male athletes had higher left and right ventricular volumes and masses in both adult ( n = 215 (145 male); 24 ± 5 years old) and adolescent ( n = 112 (97 male); 16 ± 1 years old) groups compared with women (all P < 0.05). In adults, male sex, age, body surface area, weekly training hours, mixed and endurance sports correlated with higher ventricular volumes and masses (all P < 0.05); and a combination of age, sex, training hours, endurance and mixed sports explained 30% of the variance of the left ventricular end-diastolic volume index ( r = 0.30), right ventricular end-diastolic volume index ( r = 0.34), right ventricular mass index ( r = 0.30); and as much as 53% of the left ventricular mass index ( r = 0.53) (all P < 0.0001). In adolescents, positive correlations were found between training hours and left ventricular hypertrophy ( r = 0.39, P < 0.0001), and biventricular dilation (left ventricular end-diastolic volume r = 0.34, P = 0.0008; right ventricular end-diastolic volume r = 0.36, P = 0.0004). In adolescents, age and body surface area did not correlate with cardiac magnetic resonance parameters.

Conclusion

There are significant sex differences in the physiological adaptation of adult and adolescent athlete’s heart; and male sex, higher training volume and endurance sports are major determinants of sports adaptation in adults.
Resonating Trauma
Authors: Ebbrecht-Hartmann Tobias
Published: August 2019

The participation of two members of the German radical Left terrorist group Revolutionary Cells turned the 1976 Entebbe hostage crisis into a significant chapter of German and Israeli history. The article reviews the framing of the hijacking of a passenger plane by a West German–Palestinian commando and explores historical references to the traumatic memories of the Holocaust that resonated in the public perception, cinematic depiction, and commemoration of the event. Through an analysis of newspaper coverage, documentary reports, docudrama films, and attempted attacks on German theaters, the article describes the framing as alternating and conflicting and emphasizes the relationship of history, media, and memory.
From Authenticity to Profilicity
Authors: D’Ambrosio Paul J. , Moeller Hans-Georg
Published: August 2019

Roberto Simanowski’s work reflects on how the internet transforms understandings of ourselves, others, and the world—or our “identity.” Three concepts inform his analysis: instant selves, the idea that algorithms automatically create narratives for the self; episodic selves, living as tourists from one experience to the next; and Facebook eye, seeing the world in terms of garnering “likes.” These notions point to a deeper change in identity construction that is undermining the age of authenticity. In an age of profile-based identity or “profilicity,” society operates with second-order observation, generating a need to present oneself with an appeal to general peer groups, which vary by forum. Critiques of the online world that Simanowski and others articulate tend to neglect the larger social environment and focus too narrowly on the internet while applying a somewhat anachronistic authenticity-based theoretical framework.
The molecular mechanisms mediating mammalian fertilization
Authors: Bhakta Hanisha H. , Refai Fares H. , Avella Matteo A.
Published: August 2019

Fertilization is a key biological process in which the egg and sperm must recognize one another and fuse to form a zygote. Although the process is a continuum, mammalian fertilization has been studied as a sequence of steps: sperm bind and penetrate through the zona pellucida of the egg, adhere to the egg plasma membrane and finally fuse with the egg. Following fusion, effective blocks to polyspermy ensure monospermic fertilization. Here, we review how recent advances obtained using genetically modified mouse lines bring new insights into the molecular mechanisms regulating mammalian fertilization. We discuss models for these processes and we include studies showing that these mechanisms may be conserved across different mammalian species.