bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardinalfishes (Apogonidae) show visual system adaptations typical of nocturnally and diurnally active fish
Authors: Luehrmann Martin , Carleton Karen L. , Cortesi Fabio , Cheney Karen L. , Marshall N. Justin
Published: April 2019

Animal visual systems adapt to environmental light on various timescales. In scotopic conditions, evolutionary time‐scale adaptations include spectral tuning to a narrower light spectrum, loss (or inactivation) of visual genes, and pure‐rod or rod‐dominated retinas. Some fishes inhabiting shallow coral reefs may show activity during the day and at night. It is unclear whether these fishes show adaptations typical of exclusively nocturnal or deep‐sea fishes, or of diurnally active shallow‐water species. Here, we investigated visual pigment diversity in cardinalfishes (Apogonidae). Most cardinalfishes are nocturnal foragers, yet they aggregate in multispecies groups in and around coral heads during the day, engaging in social and predator avoidance behaviours. We sequenced retinal transcriptomes of 28 species found on the Great Barrier Reef, assessed the diversity of expressed opsin genes and predicted the spectral sensitivities of resulting photopigments using sequence information. Predictions were combined with microspectrophotometry (MSP) measurements in seven cardinalfish species. Retinal opsin expression was rod opsin (RH1) dominated (>87%), suggesting the importance of scotopic vision. However, all species retained expression of multiple cone opsins also, presumably for colour vision. We found five distinct quantitative expression patterns among cardinalfishes, ranging from short‐wavelength‐shifted to long‐wavelength‐shifted. These results indicate that cardinalfishes are both well adapted to dim‐light conditions and have retained a sophisticated colour vision sense. Other reef fish families also show both nocturnal and diurnal activity while most are strictly one or the other. It will be interesting to compare these behavioural differences across different phylogenetic groups using the criteria and methods developed here.
Autopsied case with MERRF/MELAS overlap syndrome accompanied by stroke‐like episodes localized to the precentral gyrus
Authors: Miyahara Hiroaki , Matsumoto Shinjiro , Mokuno Kenji , Dei Rika , Akagi Akio , Mimuro Maya , Iwasaki Yasushi , Yoshida Mari
Published: April 2019

We present an autopsied case with A8344G‐mutated myoclonus epilepsy with ragged red fibers (MERRF)/mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes (MELAS) overlap syndrome accompanied by stroke‐like episodes localized to the precentral gyrus. A 16‐year‐old Japanese woman suddenly experienced repetitive consciousness disturbances with increased serum lactate and creatine kinase levels. Magnetic resonance imaging showed abnormal intensity of bilateral precentral gyrus. She was clinically diagnosed as having a mitochondrial disorder and the A8344G mutation was detected in mitochondrial DNA. At 17 years of age, she died from congestive heart failure secondary to a third episode of lactic acidosis. Neuropatho‐logically, multifocal laminar necrosis, which is responsible for stroke‐like episodes in MELAS, was seen in the frontal cortex including the precentral gyrus, but there was no neuronal loss and gliosis in the basal ganglia, cerebellum, and brainstem, which were compatible with MERRF. Hypertrophy of the vascular smooth muscle and choroidal epithelium were seen, and were strongly visualized by an anti‐mitochondrial antibody. Skeletal muscles showed uneven muscular diameters, increased central nuclei, and ragged red fibers (RRFs). Decreased cytochrome c oxidase (COX) activity and strongly succinate dehydrogenase (SDH)‐reactive blood vessels were also noted. Stroke‐like episodes in MERRF/MELAS overlap syndrome are thought to be rare in the frontal cortex including the precentral gyrus. Only two cases of MERRF/MELAS overlap syndrome with A8344G mutation, including this case, have shown stroke‐like episodes in the frontal lobes. Other than the A8344G mutation and frontal lobe involvement, they had a high degree of similarity in terms of presence of RRFs, gastrointestinal dysfunction, and lack of typical MERRF neuropathology. In conclusion, this is an important case describing the clinical spectrum associated with A8344G‐mutated MERRF/MELAS overlap syndrome.
Weight loss variability with SGLT2 inhibitors and GLP‐1 receptor agonists in type 2 diabetes mellitus and obesity: Mechanistic possibilities
Authors: Brown Emily , Wilding John P.H. , Barber Thomas M. , Alam Uazman , Cuthbertson Daniel J.
Published: April 2019

We are facing a global epidemic of obesity and type 2 diabetes. Weight loss, in the context of obesity and type 2 diabetes, may improve glycaemic control and weight‐related comorbidities, and in some cases, induce diabetes remission. Although lifestyle‐based weight loss strategies may be initially successful, most are not effective long‐term. There is an increasing need to consider pharmacological approaches to assist weight loss in diabetes‐obesity. Older glucose‐lowering agents may cause weight gain, whereas the newer drug classes, sodium‐glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide receptor agonists (GLP‐1 RAs), concomitantly target weight loss and glycaemic control. Clinical trial data suggest that both SGLT2i and GLP1 RAs cause a mean weight loss of approximately 2 to 3 kg but real‐world evidence and clinical experience suggests a significant heterogeneity in the magnitude of the weight loss (GLP‐1 RAs) or the magnitude of the actual weight loss is significantly less than anticipated (SGLT2i). Why do some individuals lose more weight than others in response to these pharmacological treatments? This review will first explore mechanisms by which body weight is regulated through control of energy balance and its dysregulation in obesity, and then consider how these mechanisms may be modulated therapeutically with SGLT2i and GLP1 RAs.
Aortic conduit aneurysm and enteric fistula formation in a post–liver transplant patient: A potential causative role for cytomegalovirus?
Authors: King Dominic , Neil Desley , Forde Colm , Mirza Darius , Mergental Hynek , Elsharkawy Ahmed M
Published: April 2019

Hepatic arterial aortic conduits can be used as an alternative means of revascularizing the donor liver when the native recipient hepatic artery (HA) cannot be used. Cytomegalovirus (CMV) is a common Herpesviridae infection in patients who have undergone solid organ transplants. It can be asymptomatic but may cause fever and invasive disease affecting any organ system. Here we describe the first case in the literature of an aortic conduit aneurysm and concurrent CMV viremia following liver transplantation. We speculate on a causative role for CMV in the development of the aneurysm.
Disoriented geographies: Undoing relations, encountering limits
Authors: Bissell David , Gorman‐Murray Andrew
Published: April 2019

This paper develops the concept of disorientation as a constitutive but overlooked dimension of mobile life, and it explores the significance of disorientation for geographical thought. Conceptually, the paper argues that disorientation is a productive geographical concept for acknowledging how, at times, bodies can lose their orienting relations to other bodies, to actions, and to situations. These losses are explored through the themes of incomprehension, confusion, and disintegration, respectively. Substantively, through research with mobile worker households in Australia, the paper expands our understanding of geographies of mobility by interrogating non‐traditional but increasingly common living scenarios created by intensified mobility. Methodologically, the paper develops a narrative approach to presenting the richly complex experiences of “left behind” mobile worker partners through impressionistic interview portraits. Disciplinarily, contributing to ongoing debates in geography on relationality and encounter, the paper provides a counterbalance to the dominant focus on relation construction, and it opens up space for thinking differently about what, exactly, is being encountered in disorienting experiences.
Platelet‐derived extracellular vesicles convey mitochondrial DAMPs in platelet concentrates and their levels are associated with adverse reactions
Authors: Marcoux Genevieve , Magron Audrey , Sut Caroline , Laroche Audree , Laradi Sandrine , Hamzeh‐Cognasse Hind , Allaeys Isabelle , Cabon Ophelie , Julien Anne‐Sophie , Garraud Olivier , Cognasse Fabrice , Boilard Eric
Published: April 2019

BACKGROUND

Whereas platelet transfusion is a common medical procedure, inflammation still occurs in a fraction of transfused individuals despite the absence of any apparent infectious agents. Platelets can shed membrane vesicles, called extracellular vesicles (EVs), some of which contain mitochondria (mito+EV). With its content of damage‐associated molecular pattern (DAMP), the mitochondrion can stimulate the innate immune system. Mitochondrial DNA (mtDNA) is a recognized DAMP detected in the extracellular milieu in numerous inflammatory conditions and in platelet concentrates. We hypothesized that platelet‐derived mitochondria encapsulated in EVs may represent a reservoir of mtDNA.

STUDY DESIGN AND METHODS

Herein, we explored the implication of mito+EVs in the occurrence of mtDNA quantified in platelet concentrate supernatants that induced or did not induce transfusion adverse reactions.

RESULTS

We observed that EVs were abundant in platelet concentrates, and platelet‐derived mito+EVs were more abundant in platelet concentrates that induced adverse reactions. A significant correlation (rs = 0.73; p < 0.0001) between platelet‐derived mito+EV levels and mtDNA concentrations was found. However, there was a nonsignificant correlation between the levels of EVs without mitochondria and mtDNA concentrations (rs = −0.11; p = 0.5112). The majority of the mtDNA was encapsulated into EVs.

CONCLUSION

This study suggests that platelet‐derived EVs, such as those that convey mitochondrial DAMPs, may be a useful biomarker for the prediction of potential risk of adverse transfusion reactions. Moreover, our work implies that investigations are necessary to determine whether there is a causal pathogenic role of mitochondrial DAMP encapsulated in EVs as opposed to mtDNA in solution.
A new species of the genus Stigmaeus Koch (Acari: Stigmaeidae) from the Aegean region of Turkey
Authors: AKYOL Mustafa
Published: April 2019

A new species viz. Stigmaeus dogani sp. nov., collected from soil and litter under Juncus sp. (Juncaceae) and Pinus brutia (Pinaceae) in Denizli and Izmir provinces (the Aegean region of Turkey), is described and illustrated based on adult females. A key to the species of Stigmaeus from Turkey is provided.
Heterogeneous ice nucleation correlates with bulk-like interfacial water
Authors: Wu Shuwang , He Zhiyuan , Zang Jinger , Jin Shenglin , Wang Zuowei , Wang Jianping , Yao Yefeng , Wang Jianjun
Published: April 2019

Bulk-like interfacial water, a sub-ensemble of interfacial water, can be a predictor for heterogeneous ice nucleation.
Homogeneous guiding deposition of sodium through main group II metals toward dendrite-free sodium anodes
Authors: Zhu Mengqi , Li Songmei , Li Bin , Gong Yongji , Du Zhiguo , Yang Shubin
Published: April 2019

Controllable nucleation and growth of metallic sodium are achieved via main group II metals.
Quantum localization bounds Trotter errors in digital quantum simulation
Authors: Heyl Markus , Hauke Philipp , Zoller Peter
Published: April 2019

A many-body localization phenomenon boosts the accuracy of digital quantum simulation on quantum computers.
Folding a focalized acoustical vortex on a flat holographic transducer: Miniaturized selective acoustical tweezers
Authors: Baudoin Michael , Gerbedoen Jean-Claude , Riaud Antoine , Matar Olivier Bou , Smagin Nikolay , Thomas Jean-Louis
Published: April 2019

Selective manipulation of micrometric objects in a standard microscopy environment is possible with miniaturized acoustical tweezers.
Relativistic independence bounds nonlocality
Authors: Carmi Avishy , Cohen Eliahu
Published: April 2019

Locality of uncertainty relations can explain why quantum nonlocality is the way it is.
A Novel, Widespread
qacA
Allele Results in Reduced Chlorhexidine Susceptibility in
Staphylococcus epidermidis
Authors: Addetia Amin , Greninger Alexander L. , Adler Amanda , Yuan Shuhua , Makhsous Negar , Qin Xuan , Zerr Danielle M.
Published: April 2019

Chlorhexidine gluconate (CHG) is a topical antiseptic widely used in health care settings. In
Staphylococcus
spp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution.
Infections Caused by Group C and G Streptococcus (Streptococcus dysgalactiaesubsp.equisimilisand Others): Epidemiological and Clinical Aspects
Authors: Baracco Gio J.
Published: April 2019

Streptococci carrying serogroup C and G antigens, and in particular,Streptococcus dysgalactiaesubsp.equisimilis(SDSE), are emerging human pathogens that are increasingly isolated from patients with a myriad of infections that range from mundane to life-threatening. SDSE is microbiologically similar toStreptococcus pyogenes. These streptococci frequently cause infections of the throat and skin and soft tissues. Moreover, they may invade the bloodstream and disseminate widely to many deep tissue sites, including the endocardium. Life-threatening invasive infections due to SDSE, including the streptococcal toxic shock syndrome, occur most frequently in patients with severe underlying medical diseases. Treatment with penicillin is adequate under most circumstances, but treatment failure occurs. SDSE may also be resistant to other antibiotic classes including tetracyclines, macrolides, and clindamycin. Most human infections caused by groups C and G streptococci are transmitted from person to person, but infections due toStreptococcus equisubsp.zooepidemicus(and, rarely, toS. equisubsp.equi) are zoonoses. Transmission of these latter species occurs by animal contact or by contamination of food products and has been associated with the development of poststreptococcal glomerulonephritis. Members of theStreptococcus anginosusgroup, usually classified with the viridans group of streptococci, are associated with a variety of pyogenic infections.
Streptococcus pneumoniae
Capsular Polysaccharide
Authors: Paton James C. , Trappetti Claudia
Published: April 2019

The polysaccharide capsule of
Streptococcus pneumoniae
is the dominant surface structure of the organism and plays a critical role in virulence, principally by interfering with host opsonophagocytic clearance mechanisms. The capsule is the target of current pneumococcal vaccines, but there are 98 currently recognised polysaccharide serotypes and protection is strictly serotype-specific. Widespread use of these vaccines is driving changes in serotype prevalence in both carriage and disease. This chapter summarises current knowledge on the role of the capsule and its regulation in pathogenesis, the mechanisms of capsule synthesis, the genetic basis for serotype differences, and provides insights into how so many structurally distinct capsular serotypes have evolved. Such knowledge will inform ongoing refinement of pneumococcal vaccination strategies.
Influence of weight status in the response to Step-2 maintenance therapies in children with asthma
Authors: Longo Cristina , Bartlett Gillian , Schuster Tibor , Ducharme Francine M. , MacGibbon Brenda , Barnett Tracie A.
Published: April 2019

Introduction

Overweight children with asthma may display impaired response to inhaled corticosteroids (ICS), possibly due to non-eosinophilic inflammation or weight-related lung compression; these mechanisms may differentially affect response to ICS and leukotriene receptor antagonists (LTRAs). We assessed whether weight status modified the response to low-dose ICS and LTRA Step-2 monotherapy.

Methods

A historical cohort study from clinical data linked to administrative databases was conducted among children aged 2–18 years with specialist-diagnosed asthma who were initiating or continuing a Step-2 monotherapy from 2000 to 2007 at the Montreal Children’s Hospital Asthma Centre. The outcome was time-to-management failure defined as any step-up in therapy, acute care visit, hospitalisation or oral corticosteroids for asthma, whichever occurred first. The independent and joint effects of weight status (body mass index [BMI] percentile) and time-varying treatment on time-to-management failure were estimated with marginal structural Cox models. The likelihood ratio test (LRT) and relative excess risk due to interaction (RERI) were computed to assess treatment effect modification by weight status on the multiplicative and additive scales.

Results

Of the 433 and 85 visits with a low-dose ICS and LTRA prescription, respectively, 388 management failures occurred over 14 529 visit-weeks of follow-up. Children using LTRA compared with low-dose ICS tended to have an overall higher risk of early management failure (HR 1.52; 95% CI 0.72 to 3.22). Irrespective of treatment, the hazard of management failure increased by 5% (HR 1.05; 95% CI 1.01 to 1.10) for every 10-unit increase in BMI percentile. An additional hazard reduction of 17% (HR 0.83; 95% CI 0.70 to 0.99) was observed for every 10-unit increase in BMI percentile among LTRA users, but not for ICS (HR 0.95; 95% CI 0.86 to 1.04). The LRT indicated a departure from exact multiplicativity (p<0.0001), and the RERIs for ICS and LTRA were −0.05 (95% CI −0.14 to 0.05) and −0.52 (95% CI −1.76 to 0.71).

Conclusions

Weight status was associated with earlier time-to-management failure in children prescribed Step-2 therapy. This hypothesis-generating study suggests that LTRA response increases in children with higher BMI percentiles, although further research is warranted to confirm findings.
Randomised Ambulatory Management of Primary Pneumothorax (RAMPP): protocol of an open-label, randomised controlled trial
Authors: Hallifax Rob , Laskawiec-Szkonter Magda , Dobson Melissa , Gerry Stephen , Miller Robert F , Harvey John E , Rahman Najib
Published: April 2019

Introduction

Pneumothorax is a common clinical problem. Primary spontaneous pneumothorax (PSP) occurs in otherwise fit young patients, but optimal management is not clearly defined and often results in a long hospital stay. Ambulatory treatment options are available, but the existing data on their efficacy are poor. The Randomised Ambulatory Management of Primary Pneumothorax trial is a multicentre, randomised controlled trial comparing ambulatory management with standard care, specifically designed to safely and effectively reduce hospital stay.

Methods and analysis

236 patients with PSP will be recruited from UK hospitals. Patients will be randomised 1:1 to treatment to either the ‘Intervention’ arm (ambulatory device; Rocket Pleural Vent) or the ‘Control’ arm (aspiration ± standard chest drain insertion). Patients will be followed up for a total of 12 months to assess recurrence rates. The primary outcome is total length of stay in hospital (including readmissions) up to 30 days postrandomisation. The secondary outcomes are pain and breathlessness scores, air leak measurement and radiological evidence (on CT scanning) of emphysema-like changes, compared with short-term and long-term outcomes, respectively, and health economic analysis.

Ethics and dissemination

The trial has received ethical approval from the National Research Ethics Service Committee South-Central Oxford A (15/SC/0240).

Trial registration number

ISRCTN79151659
Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883)
Authors: Hauke Jan , Hahnen Eric , Schneider Stephanie , Reuss Alexander , Richters Lisa , Kommoss Stefan , Heimbach André , Marmé Frederik , Schmidt Sandra , Prieske Katharina , Gevensleben Heidrun , Burges Alexander , Borde Julika , De Gregorio Nikolaus , Nürnberg Peter , El-Balat Ahmed , Thiele Holger , Hilpert Felix , Altmüller Janine , Meier Werner , Dietrich Dimo , Kimmig Rainer , Schoemig-Markiefka Birgid , Kast Karin , Braicu Elena , Baumann Klaus , Jackisch Christian , Park-Simon Tjoung-Won , Ernst Corinna , Hanker Lars , Pfisterer Jacobus , Schnelzer Andreas , du Bois Andreas , Schmutzler Rita K , Harter Philipp
Published: April 2019

Background

For individuals with ovarian cancer (OC), therapy options mainly depend on BRCA1/2 germline status. What is the prevalence of deleterious somatic variants, that is, does genetic tumour testing identify subgroups of individuals who also might benefit from targeted therapy?

Methods

Paired analysis of tumour-derived versus blood-derived DNA to determine the prevalence of deleterious somatic variants in OC predisposition genes (ATM, BRCA1/2, BRIP1, MSH2/6, PALB2, RAD51C/D and TP53) and the PIK3CA and PTEN genes in individuals with OC (AGO-TR1 study, NCT02222883). Results were complemented by BRCA1, PALB2 and RAD51C promoter methylation analyses and stratified by histological subtype; 473 individuals were included.

Results

The combined analyses revealed that deleterious germline variants in established OC predisposition genes (all: 125/473, 26.4%; BRCA1/2: 97/473, 20.5%), deleterious somatic variants in established OC predisposition genes excluding TP53 (all: 39/473, 8.2%; BRCA1/2: 30/473, 6.3%) and promoter methylation (all: 67/473, 14.2%; BRCA1: 57/473, 12.1%; RAD51C: 10/473, 2.1%; PALB2: 0/473) were mutually exclusive, with a few exceptions. The same holds true for deleterious somatic PIK3CA and/or PTEN variants (33/473, 7.0%) found to be enriched in endometrioid and clear cell OC (16/35, 45.7%); 84.3 % of the deleterious single-nucleotide/indel germline variants in established OC predisposition genes showed significantly higher variant fractions (VFs) in the tumour-derived versus blood-derived DNA, indicating a loss of the wild-type alleles.

Conclusion

Tumour sequencing of the BRCA1, BRCA2, PIK3CA and PTEN genes along with BRCA1 and RAD51C promoter methylation analyses identified large subgroups of germline mutation-negative individuals who may be addressed in interventional studies using PARP or PI3K/AKT/mTOR inhibitors.

Trial registration number

NCT02222883
Injuries associated with long working hours among employees in the US mining industry: risk factors and adverse outcomes
Authors: Friedman Lee S , Almberg Kirsten S , Cohen Robert A
Published: April 2019

Objectives

The mining industry is increasingly adopting extended workdays of 10–12 hour shifts. Studies demonstrate that long work hours are associated with psychomotor impairments caused by fatigue and an increased risk of injury. However, studies involving miners remain limited. This analysis aimed to identify risk factors associated with long working hour injuries and to determine if long working hour incidents were associated with being killed or incidents involving multiple injured workers.

Methods

Data from US Mine Safety and Health Administration Part 50 reports, 1983–2015, were used to identify long working hour injuries, which were defined as incidents occurring nine or more hours after the start of a shift.

Results

A total of 52 206 injuries (9.6%) occurred during long working hours. The proportion of long working hour injuries increased from 5.5% of all injuries in 1983 to its peak in 2015 at 13.9% (p<0.001). Risk factors associated with long working hour injuries included irregular shift starts, being newly employed, employment by a contractor, metal/non-metal operations and mines with <100 employees. In two separate adjusted models, long working hour injuries were associated with a higher odds of death (adjusted OR [aOR]=1.32; 95% CI 1.18 to 1.48) and single incidents resulting in two or more workers injured (aOR=1.73; 95% CI 1.58 to 1.89).

Conclusions

Long working hour injuries were associated with a lack of routine, being new at the mine and specific mining activities. An international shift towards using contract labour and extended workdays indicates that injuries during long working hours will likely continue to grow as a problem in the mining industry.
A zero coronary artery calcium score in patients with stable chest pain is associated with a good prognosis, despite risk of non-calcified plaques
Authors: Wang Xue , Le Elizabeth Phuong Vi , Rajani Nikil K , Hudson-Peacock NJ , Pavey Holly , Tarkin Jason M , Babar Judith , Williams Michelle Claire , Gopalan Deepa , Rudd James H F
Published: April 2019

Objectives

To estimate the prevalence of non-calcified coronary artery disease (CAD) in patients with suspected stable angina and a zero coronary artery calcification (CAC) score, and to assess the prognostic significance of a zero CAC in these symptomatic patients.

Methods

In this prospective cohort study, consecutive patients with stable chest pain underwent CAC scoring ± CT coronary angiography (CTCA) as part of routine clinical care at a single tertiary centre over 7 years. Major adverse cardiac event (MACE) was defined as cardiac death, non-fatal myocardial infarction and/or non-elective revascularisation.

Results

A total of 915 of 1753 (52.2%) patients (mean age 56.8 ± 12.0 years; 46.2% male) had a zero CAC score. Of the 751 (82.1%) patients with a zero CAC in whom CTCA was performed, 674 (89.7%) had normal coronary arteries, 63 (8.4%) had non-calcified CAD with < 50% stenosis and 14 (1.9%) had ≥ 50% stenosis in at least one coronary artery. The negative predictive value of a zero CAC for excluding a ≥ 50% CTCA stenosis was 98.1%. Over a median follow-up period of 2.2 years (range 1.0–7.0 years), the absolute annualised rates of MACE were as follows: zero CAC 1.9 per 1000 person-years and non-zero CAC 7.4 per 1000 person-years (HR 3.8, p = 0.009). However, after adjusting for age, gender and cardiovascular risk factors using a multivariable Cox proportional hazards model, there was no statistically significant difference in the risk of MACE between the two patient cohorts (p = 0.19). After adjusting for age, gender and cardiovascular risk factors, the HR for all-cause mortality among the zero CAC cohort vers non-zero CAC was 2.1 (p = 0.27).

Conclusion

A zero CAC score in patients undergoing CT scanning for suspected stable angina has a high negative predictive value for the exclusion of obstructive CAD and is associated with a good medium-term prognosis.
Curcumin Promotes Connexin 43 Degradation and Temozolomide-Induced Apoptosis in Glioblastoma Cells
Authors: Huang Bor-Ren , Tsai Chon-Haw , Chen Chun-Chuan , Way Tzong-Der , Kao Jung-Yie , Liu Yu-Shu , Lin Hsiao-Yun , Lai Sheng-Wei , Lu Dah-Yuu
Published: April 2019

Glioblastoma (GBM) is the most commonly occurring tumor in the cerebral hemispheres. Currently, temozolomide (TMZ), an alkylating agent that induces DNA strand breaks, is considered the frontline chemotherapeutic agent for GBM. Despite its frontline status, GBM patients commonly exhibit resistance to TMZ treatment. We have recently established and characterized TMZ-resistant human glioma cells. The aim of this study is to investigate whether curcumin modulates cell apoptosis through the alternation of the connexin 43 (Cx43) protein level in TMZ-resistant GBM. Overexpression of Cx43, but not ATP-binding cassette transporters (ABC transporters), was observed (approximately 2.2-fold) in TMZ-resistant GBM cells compared to the Cx43 levels in parental GBM cells. Furthermore, at a concentration of 10[Formula: see text][Formula: see text]M, curcumin significantly reduced Cx43 protein expression by about 40%. In addition, curcumin did not affect the expression of other connexins like Cx26 or epithelial-to-mesenchymal transition (EMT) proteins such as [Formula: see text]-catenin or [Formula: see text]E-catenin. Curcumin treatment led to an increase in TMZ-induced cell apoptosis from 4% to 8%. Importantly, it did not affect the mRNA expression level of Cx43. Concomitant treatment with the translation inhibitor cycloheximide (CHX) exerted additional effects on Cx43 degradation. Treatment with the autophagy inhibitor 3-MA (methyladenine) did not affect the curcumin-induced Cx43 degradation. Interestingly, treatment with the proteasome inhibitor MG132 (carbobenzoxy-Leu-Leu-leucinal) significantly negated the curcumin-induced Cx43 degradation, which suggests that curcumin-induced Cx43 degradation occurs through the ubiquitin-proteasome pathway.
Black hole solution of Gauss–Bonnet-massive gravity coupled to nonlinear Maxwell and Yang–Mills fields in higher dimensions
Authors: Li Jun , Meng Kun
Published: April 2019

We construct a static black hole solution of Gauss–Bonnet-massive gravity coupled to nonlinear Maxwell and Yang–Mills fields in higher dimensions. Then we calculate related thermodynamic quantities, check the validity of the first law of black hole thermodynamics and analyze the phase transition behaviors of the black hole in extended phase space.
Evaluation of carrier lifetime and photocatalytic properties of annealed ZnS/TiO2 nanocomposite
Authors: Ohara Tomoya , Furube Akihiro , Koinkar Pankaj , Patil Deepak
Published: April 2019

In this study, zinc sulfide (ZnS)/titanium oxide(TiO2) nanoparticles were prepared by a two-step facile hydrothermal method and then annealing at [Formula: see text] for 30 min. Also, the transient absorption measurement and photocatalytic activity of ZnS/TiO2 before and after annealing were investigated. The characterization technique such as the scanning electron microscopy (SEM) and X-ray diffraction (XRD) and UV–Visible spectroscopy have been employed to study the surface morphology and structural details. The SEM image shows the change in the surface morphology due to annealing. The change of the crystal structure of ZnS–TiO2 is revealed by XRD spectra. The femtosecond transient absorption measurement showed moderate decay over several hundred picoseconds for annealed ZnS/TiO2. Moreover, improved photocatalytic activity of annealed ZnS/TiO2 nanoparticles in visible light has been observed.
Systems Approaches to Materials Design: Past, Present, and Future
Authors: Arróyave Raymundo , McDowell David L.
Published: April 2019

There is increasing awareness of the imperative to accelerate materials discovery, design, development, and deployment. Materials design is essentially a goal-oriented activity that views the material as a complex system of interacting subsystems with models and experiments at multiple scales of materials structure hierarchy. The goal of materials design is effectively to invert quantitative relationships between process path, structure, and materials properties or responses to identify feasible materials. We first briefly discuss challenges in framing process-structure-property relationships for materials and the critical role of quantifying uncertainty and tracking its propagation through analysis and design. A case study exploiting inductive design of ultrahigh-performance concrete is briefly presented. We focus on important recent directions and key scientific challenges regarding the highly collaborative intersections of materials design with systems engineering, uncertainty quantification and management, optimization, and materials data science and informatics, which are essential to fueling continued progress in systems-based materials design.
Effects of high-intensity interval training on microvascular glycocalyx and associated microRNAs
Authors: Schmitz Boris , Niehues Hannah , Lenders Malte , Thorwesten Lothar , Klose Andreas , Krüger Michael , Brand Eva , Brand Stefan-Martin
Published: April 2019

High-intensity interval training (HIIT) has been proposed to exert vasculoprotective effects. This study aimed to evaluate whether HIIT affects the microvasculature, including the endothelial glycocalyx barrier, and to identify associated microRNAs (miRNAs). Fifty healthy participants (23.1 ± 3.0 yr) performed a 4-wk 4 × 30-s all-out running HIIT. Sidestream dark-field imaging was performed at baseline and follow-up to detect changes of the sublingual microvasculature including the endothelial glycocalyx. Exercise parameters were determined by continuous running field test and documentation of high-intensity runs. miRNAs potentially associated with glycocalyx thickness were selected by structured literature search and blood samples for miRNA, and lactate measurements were drawn at baseline and follow-up HIIT. At baseline, a correlation between maximal exercise performance capacity and glycocalyx thickness (determined by perfused boundary region) was detected ( P = 0.045, r = 0.303). Increased exercise performance at follow-up also correlated with glycocalyx thickness ( P = 0.031, r = 0.416), and increased high-intensity sprinting speed was associated with an increased number of perfused vessels ( P = 0.0129, r = 0.449). Literature search identified miR-143, -96-5p, and -24, which were upregulated by HIIT already at baseline and showed an association with peak blood lactate levels after sprints (all P < 0.05). Moreover, increased baseline miR-143 levels predicted increased glycocalyx thickness at follow-up (AUCmiR-143 = 0.92, 95% confidence interval, 0.81–1.0, P = 0.0008). Elevated resting miR-126 levels after the intervention were associated with cell-free versican mRNA levels. We conclude that HIIT induces changes in the endothelial glycocalyx of the microvasculature. Associated miRNAs such as miR-143 may represent a tool for monitoring early vasculoprotective adaptations to physical activity.

NEW & NOTEWORTHY High-intensity interval training is known to improve health-related fitness in general and in lifestyle-induced chronic diseases. To visualize microvasculature structure and to detect exercise-induced changes, sublingual sidestream dark-field imaging microscopy was used, and circulating miRNAs were measured. This study shows that exercise-induced changes correlate with associated circulating miRNA, which might be useful for monitoring vasculoprotective effects. Furthermore, sidestream dark-field imaging may represent a sensitive tool for the early detection of exercise-induced systemic vascular changes.
Combined CD28 and 4-1BB Costimulation Potentiates Affinity-tuned Chimeric Antigen Receptor–engineered T Cells
Authors: Drent Esther , Poels Renée , Ruiter Ruud , van de Donk Niels W.C.J. , Zweegman Sonja , Yuan Huipin , de Bruijn Joost , Sadelain Michel , Lokhorst Henk M. , Groen Richard W.J. , Mutis Tuna , Themeli Maria
Published: April 2019

Purpose:

Targeting nonspecific, tumor-associated antigens (TAA) with chimeric antigen receptors (CAR) requires specific attention to restrict possible detrimental on-target/off-tumor effects. A reduced affinity may direct CAR-engineered T (CAR-T) cells to tumor cells expressing high TAA levels while sparing low expressing normal tissues. However, decreasing the affinity of the CAR-target binding may compromise the overall antitumor effects. Here, we demonstrate the prime importance of the type of intracellular signaling on the function of low-affinity CAR-T cells.

Experimental Design:

We used a series of single-chain variable fragments (scFv) with five different affinities targeting the same epitope of the multiple myeloma–associated CD38 antigen. The scFvs were incorporated in three different CAR costimulation designs and we evaluated the antitumor functionality and off-tumor toxicity of the generated CAR-T cells in vitro and in vivo.

Results:

We show that the inferior cytotoxicity and cytokine secretion mediated by CD38 CARs of very low–affinity (Kd < 1.9 × 10−6 mol/L) bearing a 4-1BB intracellular domain can be significantly improved when a CD28 costimulatory domain is used. Additional 4-1BB signaling mediated by the coexpression of 4-1BBL provided the CD28-based CD38 CAR-T cells with superior proliferative capacity, preservation of a central memory phenotype, and significantly improved in vivo antitumor function, while preserving their ability to discriminate target antigen density.

Conclusions:

A combinatorial costimulatory design allows the use of very low–affinity binding domains (Kd < 1 μmol/L) for the construction of safe but also optimally effective CAR-T cells. Thus, very-low-affinity scFvs empowered by selected costimulatory elements can enhance the clinical potential of TAA-targeting CARs.
Erfolgreiche therapeutische endoskopisch-endoluminale Procaininstillation in eine Anastomosenregion bei chronischem Symptomkomplex nach operativer Versorgung einer angeborenen Ösophagusatresie
Authors: Schotes Sarah , Saha Felix Joyonto , Langhorst Jost
Published: April 2019

Hintergrund: Wir berichten über eine 27-jährige Patientin, die nach operativem Magenhochzug bei Ösophagusatresie unter massiv einschränkenden Symptomen wie Sodbrennen, Erbrechen, Regurgitation, Übelkeit und Magenkrämpfen litt, trotz maximaler konservativer Therapie. Falldarstellung: Die Patientin erhielt im Rahmen einer Gastroskopie eine endoluminale Procaininfiltration in die narbige Anastomosenregion, woraufhin sich die klinische Symptomatik deutlich reduzierte und auch im Langzeitverlauf stabil vermindert blieb. Schlussfolgerung: Wir beschreiben die unseres Wissens nach erste endoluminale Infiltration von Procain in narbige Gewebsareale einer enteralen Anastomosenregion nach operativem Magenhochzug.
Analyses for Prevalence and Outcome of Tricuspid Regurgitation in China: An Echocardiography Study of 134,874 Patients
Authors: Yang Lifan , Chen Haiyan , Pan Wenzhi , Guan Lihua , Zhang Xiaochun , Zhang Lei , Jin Qinchun , Zhou Daxin , Shu Xianhong , Ge Junbo
Published: April 2019

Background: The aim of this study is to investigate the prevalence and outcome of tricuspid regurgitation (TR) in the Chinese population. Methods: The echocardiography database, including 134,874 patients at our heart center from 2010 to 2012, was retrospectively analyzed. Results: The rates of mild, moderate, and severe TR were 2.96, 2.22, and 1.39%, respectively. Of these patients, 4.86% had primary TR, 91.41% had functional TR, and 3.73% had unexplained TR. The rate of TR was increased in elders (odds ratio: 1.038 for 1 year’s increment; 95% confidence interval: 1.037–1.040; p < 0.001) and females (odds ratio: 1.386; 95% confidence interval: 1.327–1.448, p < 0.001). The major etiologies of TR were left-sided valve heart disease (VHD) and dilated cardiomyopathy. The survival rate of severe TR patients with pulmonary artery hypertension (PAH) was lower than in those without PAH (p < 0.0001). There was a positive association between the prevalence of TR and impaired left ventricular ejection fraction. Compared to the non-left-sided VHD group, the left-sided VHD group had a better prognosis among severe TR patients. The 5-year survival rates were 79.69, 71.12, and 77.01% in the groups of left-sided VHD, non-left-sided VHD, and all patients. Conclusions: Patients with severe TR have a bad prognosis, especially those with non-left-sided VHD and those with PAH.
Social Complexity and Brain Evolution: Comparative Analysis of Modularity and Integration in Ant Brain Organization
Authors: Kamhi J. Frances , Ilieş Iulian , Traniello James F.A.
Published: April 2019

The behavioral demands of living in social groups have been linked to the evolution of brain size and structure, but how social organization shapes investment and connectivity within and among functionally specialized brain regions remains unclear. To understand the influence of sociality on brain evolution in ants, a premier clade of eusocial insects, we statistically analyzed patterns of brain region size covariation as a proxy for brain region connectivity. We investigated brain structure covariance in young and old workers of two formicine ants, the Australasian weaver ant Oecophylla smaragdina, a pinnacle of social complexity in insects, and its socially basic sister clade Formica subsericea. As previously identified in other ant species, we predicted that our analysis would recognize in both species an olfaction-related brain module underpinning social information processing in the brain, and a second neuroanatomical cluster involved in nonolfactory sensorimotor processes, thus reflecting conservation of compartmental connectivity. Furthermore, we hypothesized that covariance patterns would reflect divergence in social organization and life histories either within this species pair or compared to other ant species. Contrary to our predictions, our covariance analyses revealed a weakly defined visual, rather than olfactory, sensory processing cluster in both species. This pattern may be linked to the reliance on vision for worker behavioral performance outside of the nest and the correlated expansion of the optic lobes to meet navigational demands in both species. Additionally, we found that colony size and social organization, key measures of social complexity, were only weakly correlated with brain modularity in these formicine ants. Worker age also contributed to variance in brain organization, though in different ways in each species. These findings suggest that brain organization may be shaped by the divergent life histories of the two study species. We compare our findings with patterns of brain organization of other eusocial insects.
The Effect of Head-Out Aquatic Exercise on Arterial Stiffness in Middle-Aged and Elderly People
Authors: Fukuie Marina , Yamabe Takayuki , Nomura Yosuke  , Hashitomi Tatsuya , Maeda Seiji , Sugawara Jun
Published: April 2019

Aquatic exercise is ideal for older adults because it mitigates weight-bearing stress. However, the effect of head-out aquatic exercise on arterial stiffness, a strong future cardiovascular disease (CVD) risk, remains unclear. We determined whether head-out aquatic exercise would mitigate arterial stiffness in middle-aged and elderly people. In 25 middle-aged and older people (9 men, mean age 64 ± 8 years), blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV) were measured before and after a supervised aquatic exercise training program (60 min, 1 session/week, 14 sessions) which mainly consisted of walking, stretching, and muscle strengthening in water. In the pooled subjects, systolic BP tended to decrease (p = 0.07) after the training intervention, whereas no significant changes were observed, including baPWV (from 1,537 ± 301 to 1,496 ± 308 cm/s). In the sub-analysis, by dividing subjects into a healthy group (n = 13) and a CVD risk group (n = 12), no significant interaction between time and group was seen in BP. On the other hand, baPWV decreased significantly in the healthy group (from 1,476 ± 299 to 1,365 ± 215 cm/s) but not in the CVD risk group (from 1,603 ± 301 to 1,637 ± 339 cm/s). The current study demonstrates that regular head-out aquatic exercise, even at a low frequency, could mitigate CVD risk in apparently healthy middle-aged and older people.
Evaluating the Accuracy of the Endoscopic ABC Classification System in Diagnosing Helicobacter pylori-Infected Gastritis
Authors: Inui Masayuki , Ohwada Susumu , Inui Yoshikatsu , Kondo Yuko , Moro Amika , Sasaki Kazunari
Published: April 2019

Aims: Evaluating the accuracy of the modified Endoscopic ABC (Endo ABC) classification with an electronic endoscopy with narrow band imaging without magnification in diagnosing Helicobacter pylori (H. pylori)-infected gastritis. Methods: A total of 576 patients were enrolled and they underwent modified Endo ABC. They were stratified into 5 groups (A to E) based on the grades of endoscopic findings. H. pylori-infected gastritis status was determined in the following ways: current H. pylori gastritis was defined as active gastritis and/or chronic atrophic gastritis (CAG) seen on endoscopy and positive H. pylori test, naïve H. pylori gastritis was defined as regular arrangement of collecting venules in the angle of the lesser curvature without CAG and negative H. pylori test, and previous H. pylori gastritis was defined as negative H. pylori tests regardless of the presence of CAG. Results: Endo A has 97% accuracy and 100% positive predictive value in diagnosing naïve H. pylori gastritis. Endo E has 97% accuracy and 100% positive predictive value in diagnosing previous H. pylori gastritis. The accuracy of Endo B and Endo C in diagnosing current H. pylori gastritis was 89 and 82% respectively. Endo D has 87% accuracy in diagnosing previous H. pylori gastritis. Conclusion: This study showed that the modified Endo ABC classification enables to accurately determine the H. pylori-infected gastritis status.
Sepsis Management with a Blood Purification Membrane: European Experience
Authors: Pickkers Peter , Vassiliou Timon , Liguts Valdis , Prato Federico , Tissieres Pierre , Kloesel Stephan , Turani Franco , Popevski Dijana , Broman Marcus , Gindac Ciprian Mihai , Saliba Faouzi , Tengattini Marco , Goldstein Jacques , Harenski Kai
Published: April 2019

Background: Septic shock is a leading cause of acute kidney injury (AKI). Endotoxins and cytokine levels are associated with the occurrence and severity of AKI, and different blood purification devices are available to remove them from circulation. One such device, oXiris, is a hollow-fibre purification filter that clears both endotoxins and cytokines. Due to limited evidence, clinical use of this device is not currently advocated in guidelines. However, clinics do regularly use this device, and there is a critical need for guidance on the application of it in sepsis with and without AKI. Method: A modified Delphi-based method was used to collate ­European experts’ views on the indication(s), initiation and discontinuation criteria and success measures for oXiris. Results: A panel of 14 participants was selected based on known clinical expertise in the areas of critical care and sepsis management, as well as their experience of using the oXiris blood purification device. The participants used different criteria to initiate treatment with oXiris in sepsis patients with and without AKI. Septic shock with AKI was the priority patient population, with oXiris used to rapidly improve haemodynamic parameters. Achieving haemodynamic stability within 72 h was a key factor for determining treatment success. Conclusion: In the absence of established guidelines, users of hollow-fibre purification devices such as oXiris may benefit from standardised approaches to selecting patients and initiating and terminating treatment, as well as measuring success. Further evidence in the form of randomised clinical trials is urgently required.
Biliary Involvement in Type 2 Autoimmune Pancreatitis
Authors: Ollo Diana , Terraz Sylvain , Arnoux Gregoire , Puppa Giacomo , Frossard Jean-Louis , Bichard Philippe
Published: April 2019

Autoimmune pancreatitis (AIP) is a rare condition classified in 2 subtypes. Their distinction relies on a combination of clinical, serological, morphological and histological features. Type 1 is a pancreatic manifestation of IgG4-related disease characterized by multiorgan infiltration by IgG4 plasmocytes. In this condition, hepatobiliary infiltration is frequent and often mimics cholangiocarcinoma or primary sclerosing cholangitis. On the other hand, type 2 is commonly limited to the pancreas. Herein, we describe the case of a patient who presented a type 2 AIP associated with cholangiopathy, a condition not described in the established criteria. He first developed a pancreatitis identified as type 2 by the typical histopathological features and lack of IgG4 in the serum and tissue. Despite a good clinical response to steroids, cholestasis persisted, identified by MR cholangiography as a stricture of the left hepatic duct with dilatation of the intrahepatic bile duct in segments 2 and 3. Biliary cytology was negative. Evolution was favorable but after steroid tapering a few months later, the patient suffered from recurrence of the pancreatitis as well as progression of biliary attempt, suspicious for cholangiocarcinoma. As the investigations again ruled out neoplastic infiltration or primary sclerosing cholangitis, azathioprine was initiated with resolution of both pancreatic and biliary attempts.