bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehospital Invasive Arterial Pressure: Use of a Minimized Flush System
Authors: Karlsson Jonas , Linde Joacim , Svensen Christer , Gellerfors Mikael
Published: August 2018

Introduction

Invasive blood pressure (IBP) monitoring could be of benefit for certain prehospital patient groups such as trauma and cardiac arrest patients. However, there are disadvantages with using conventional IBP devices. These include time to prepare the transducer kit and flush system as well as the addition of long tubing connected to the patient. It has been suggested to simplify the IBP equipment by replacing the continuous flush system with a syringe and a short stopcock.

Hypothesis

In this study, blood pressures measured by a standard IBP (sIBP) transducer kit with continuous flush was compared to a transducer kit connected to a simplified and minimized flush system IBP (mIBP) using only a syringe.

Methods

A mechanical, experimental model was used to create arterial pressure pulsations. Measurements were made simultaneously using a sIBP and mIBP device, respectively. This was repeated four times using different mean arterial pressure (MAP): 40, 70, 110, and 140mm Hg. For each series, 16 measurements were taken during 20 minutes. Data were analyzed using Bland-Altman plots. Measurement error greater than five percent was regarded as clinically significant.

Results

Mean bias and standard deviation (SD) for systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP was -3.05 (SD = 2.07), 0.2 (SD = 0.48), and -0.3 (SD = 0.55) mmHg, respectively. Bland-Altman plots revealed that the bias and SD for systolic pressures was mainly due to an increased under-estimation of pressures in lower ranges. All MAP and 98.4% of diastolic pressure measurements had an error of less than five percent. Systolic pressures in the MAP 40 series all had an error of greater than five percent. All other systolic pressures had an error of less than five percent.

Conclusion

Thus, IBP with the mIBP flush system provides accurate measurement of MAP and DBP in a wide range of physiological pressures. For SBP, there was a tendency to under-estimate pressures, with larger error in lower pressures. Implementation of a simplified flush system could allow further development and potentially simplify the use of IBP for prehospital critical care teams.

KarlssonJ,LindeJ,SvensenC,GellerforsM.Prehospital invasive arterial pressure: use of a minimized flush system.Prehosp Disaster Med.2018;33(5):490–494.
Urine cultures and antibiotics for urinary tract infections in Dutch general practice
Authors: Ganzeboom Karlijn M.J. , Uijen Annemarie A. , Teunissen Doreth T.A.M. , Assendelft Willem. J.J. , Peters Hans J.G. , Hautvast Jeannine L.A. , Van Jaarsveld Cornelia H.M.
Published: August 2018

Background

Urinary tract infections (UTIs) are common in general practice, and antibiotic resistance is often seen. Urine cultures are advised by the Dutch national UTI guideline for patients at high risk of UTI complications. Prudent use of antibiotics and taking into account national guidelines and urine culture results are important to combat antibiotic resistance in general practice.

Aim

To identify subgroups of UTI patients in which the use of urine cultures and antibiotic prescriptions deviates from the national guidelines.

Methods

We investigated associations of several characteristics with urine culture orders in patients with UTI in 2015 from seven Dutch general practices (n=1295). These included subgroups at risk for UTI complications, comorbidities, age and history of UTI recurrence. In addition, we assessed the level of adherence to the guideline for antibiotic prescriptions in subgroups at risks for UTI complications.

Findings

Urine cultures were ordered in 17% (n=221) of patients, more frequently in high-risk patients (32%) than in low-risk patients (7%), for UTI complications (OR=6.4; 95% CI 4.6–9.0). In low-risk patients, 91% received antibiotics that were recommended in the guideline. For high-risk patients this percentage ranged widely, and was particularly low in the risk groups with signs of tissue invasion (29–50%). Diagnostic and therapeutic adequacy can still be improved by increasing the adherence to the guideline in UTI patients at high risk for complications. This may contribute to containing antibiotic resistance in UTI by ordering urine cultures and use the results to adjust prescriptions to antibiotic susceptibility of the uropathogen.
Evaluation of decision support tools for patients with advanced cancer: A systematic review of literature
Authors: Tapp Diane , Blais Marie-Claude
Published: August 2018

Objective

Medical decisions in the context of advanced cancer are more based on patient values and preferences than during the early stages of the disease. The implementation of shared decision-making is particularly important with an oncology palliative care population. However, few decision support tools focus on this population. This literature review aims to identify decision support tools related to palliative care for an oncological population and to assess their quality using International Patient Decision Aids Standards criteria.

Method

The tools were identified through PsycINFO, EMBASE, MEDLINE, and CINAHL databases; the inventory of tools to assist the decisions of the Ottawa Hospital Research Institute; and through the register of Cochrane trials. They were then evaluated using the third version of the International Patient Decision Aids Standards instrument.

Result

Sixteen tools were identified, which targeted five types of cancer and addressed a particular decision or the use of chemotherapy in addition to palliative care. The quality of the reviewed tools varies.

Significance of results

Clinicians can use four decision support tools related to palliative care with an oncology population that meet a certain quality standard. Further studies are needed to develop new decision support tools targeting more types of cancer and decisions.
A profile of Australian mental health carers, their caring role and service needs: results from the 2012 Survey of Disability, Ageing and Carers
Authors: Diminic S. , Hielscher E. , Harris M. G. , Lee Y. Y. , Kealton J. , Whiteford H. A.
Published: August 2018

Aims

Planning mental health carer services requires information about the number of carers, their characteristics, service use and unmet support needs. Available Australian estimates vary widely due to different definitions of mental illness and the types of carers included. This study aimed to provide a detailed profile of Australian mental health carers using a nationally representative household survey.

Methods

The number of mental health carers, characteristics of carers and their care recipients, caring hours and tasks provided, service use and unmet service needs were derived from the national 2012 Survey of Disability, Ageing and Carers. Co-resident carers of adults with a mental illness were compared with those caring for people with physical health and other cognitive/behavioural conditions (e.g., autism, intellectual disability, dementia) on measures of service use, service needs and aspects of their caring role.

Results

In 2012, there were 225 421 co-resident carers of adults with mental illness in Australia, representing 1.0% of the population, and an estimated further 103 813 mental health carers not living with their care recipient. The majority of co-resident carers supported one person with mental illness, usually their partner or adult child. Mental health carers were more likely than physical health carers to provide emotional support (68.1%v.19.7% of carers) and less likely to assist with practical tasks (64.1%v.86.6%) and activities of daily living (31.9%v.48.9%). Of co-resident mental health carers, 22.5% or 50 828 people were confirmed primary carers – the person providing the most support to their care recipient. Many primary mental health carers (37.8%) provided more than 40 h of care per week. Only 23.8% of primary mental health carers received government income support for carers and only 34.4% received formal service assistance in their caring role, while 49.0% wanted more support. Significantly more primary mental health than primary physical health carers were dissatisfied with received services (20.0%v.3.2%), and 35.0% did not know what services were available to them.

Conclusions

Results reveal a sizable number of mental health carers with unmet needs in the Australian community, particularly with respect to financial assistance and respite care, and that these carers are poorly informed about available supports. The prominence of emotional support and their greater dissatisfaction with services indicate a need to better tailor carer services. If implemented carefully, recent Australian reforms including the Carer Gateway and National Disability Insurance Scheme hold promise for improving mental health carer supports.
Sandbagging and the Self
Authors: Barnett Michael D. , Maciel Idalia V. , King Marley A.
Published: August 2018

Abstract. Sandbagging – a self-presentation strategy defined by feigned performance or false claims of inability – has been associated with lower self-esteem. The purpose of this study was to investigate whether narcissism explains the relationship between sandbagging and self-esteem. College students ( N = 813) completed a survey. Grandiose and vulnerable narcissism explained variance in sandbagging beyond what was explained by self-esteem. When grandiose or vulnerable narcissism was included, the relationship between self-esteem and sandbagging was no longer significant. Overall, the results were consistent with the notion that the relationship between lower self-esteem and sandbagging may be subsumed by narcissism.
Self–Other Differences in Decision-Making Under Risk
Authors: Lu Jingyi , Shang Xuesong , Li Bingjie
Published: August 2018

Abstract. Decisions made for others reflect not only decision-makers’ cognitive and emotional states but also decision-makers’ interpersonal concerns. People who make choices for others will potentially be blamed for unappealing outcomes by others. Therefore, we hypothesize that individuals will seek sure gains (which increase individuals’ responsibility for desirable outcomes) and avoid sure losses (which decrease individuals’ responsibility for undesirable outcomes) when making risky decisions for others more than when making such decisions for themselves. The results of two studies show that making decisions for others (vs. oneself) promotes risk-averse choices over gains. This effect may be driven by the perceived responsibility associated with different options. When both options exhibit variance in outcomes, such self–other difference disappears. However, no self–other difference over losses was observed. Taken together, our research highlights interpersonal concerns in making decisions for others, as well as the behavioral consequences of these concerns in decisions under risk.
GATA2 zinc finger 1 mutations are associated with distinct clinico-biological features and outcomes different from GATA2 zinc finger 2 mutations in adult acute myeloid leukemia
Authors: Tien Feng-Ming , Hou Hsin-An , Tsai Cheng-Hong , Tang Jih-Luh , Chiu Yu-Chiao , Chen Chien-Yuan , Kuo Yuan-Yeh , Tseng Mei-Hsuan , Peng Yen-Ling , Liu Ming-Chih , Liu Chia-Wen , Liao Xiu-Wen , Lin Liang-In , Lin Chien-Ting , Wu Shang-Ju , Ko Bor-Sheng , Hsu Szu-Chun , Huang Shang-Yi , Yao Ming , Chou Wen-Chien , Tien Hwei-Fang
Published: August 2018

Mutations of the GATA binding protein 2 (GATA2) gene in myeloid malignancies usually cluster in the zinc finger 1 (ZF1) and the ZF2 domains. Mutations in different locations of GATA2 may have distinct impact on clinico-biological features and outcomes in AML patients, but little is known in this aspect. In this study, we explored GATA2 mutations in 693 de novo non-M3 AML patients and identified 44 GATA2 mutations in 43 (6.2%) patients, including 31 in ZF1, 10 in ZF2, and three outside the two domains. Different from GATA2 ZF2 mutations, ZF1 mutations were closely associated with French-American-British (FAB) M1 subtype, CEBPA double mutations (CEBPAdouble-mut), but inversely correlated with FAB M4 subtype, NPM1 mutations, and FLT3-ITD. ZF1-mutated AML patients had a significantly longer overall survival (OS) than GATA2-wild patients and ZF2-mutated patients in total cohort as well as in those with intermediate-risk cytogenetics and normal karyotype. ZF1 mutations also predicted better disease-free survival and a trend of better OS in CEBPAdouble-mut patients. Sequential analysis showed GATA2 mutations could be acquired at relapse. In conclusion, GATA2 ZF1 mutations are associated with distinct clinico-biological features and predict better prognosis, different from ZF2 mutations, in AML patients.
Utilization of rare codon-rich markers for screening amino acid overproducers
Authors: Zheng Bo , Ma Xiaoyan , Wang Ning , Ding Tingting , Guo Liwei , Zhang Xiaorong , Yang Yu , Li Chun , Huo Yi-Xin
Published: August 2018

The translation of rare codons relies on their corresponding rare tRNAs, which could not be fully charged under amino acid starvation. Theoretically, disrupted or retarded translation caused by the lack of charged rare tRNAs can be partially restored by feeding or intracellular synthesis of the corresponding amino acids. Inspired by this assumption, we develop a screening or selection system for obtaining overproducers of a target amino acid by replacing its common codons with the corresponding synonymous rare alternative in the coding sequence of selected reporter proteins or antibiotic-resistant markers. Results show that integration of rare codons can inhibit gene translations in a frequency-dependent manner. As a proof-of-concept, Escherichia coli strains overproducing l-leucine, l-arginine or l-serine are successfully selected from random mutation libraries. The system is also applied to Corynebacterium glutamicum to screen out l-arginine overproducers. This strategy sheds new light on obtaining and understanding amino acid overproduction strains.
Biomimetic coating-free surfaces for long-term entrapment of air under wetting liquids
Authors: Domingues Eddy M. , Arunachalam Sankara , Nauruzbayeva Jamilya , Mishra Himanshu
Published: August 2018

Trapping air at the solid–liquid interface is a promising strategy for reducing frictional drag and desalting water, although it has thus far remained unachievable without perfluorinated coatings. Here, we report on biomimetic microtextures composed of doubly reentrant cavities (DRCs) and reentrant cavities (RCs) that can enable even intrinsically wetting materials to entrap air for long periods upon immersion in liquids. Using SiO2/Si wafers as the model system, we demonstrate that while the air entrapped in simple cylindrical cavities immersed in hexadecane is lost after 0.2 s, the air entrapped in the DRCs remained intact even after 27 days (~106 s). To understand the factors and mechanisms underlying this ten-million-fold enhancement, we compared the behaviors of DRCs, RCs and simple cavities of circular and non-circular shapes on immersion in liquids of low and high vapor pressures through high-speed imaging, confocal microscopy, and pressure cells. Those results might advance the development of coating-free liquid repellent surfaces.
LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat
Authors: Schmidt Elena , Dhaouadi Ines , Gaziano Isabella , Oliverio Matteo , Klemm Paul , Awazawa Motoharu , Mitterer Gerfried , Fernandez-Rebollo Eduardo , Pradas-Juni Marta , Wagner Wolfgang , Hammerschmidt Philipp , Loureiro Rute , Kiefer Christoph , Hansmeier Nils R. , Khani Sajjad , Bergami Matteo , Heine Markus , Ntini Evgenia , Frommolt Peter , Zentis Peter , Ørom Ulf Andersson , Heeren Jörg , Blüher Matthias , Bilban Martin , Kornfeld Jan-Wilhelm
Published: August 2018

Increasing brown adipose tissue (BAT) thermogenesis in mice and humans improves metabolic health and understanding BAT function is of interest for novel approaches to counteract obesity. The role of long noncoding RNAs (lncRNAs) in these processes remains elusive. We observed maternally expressed, imprinted lncRNA H19 increased upon cold-activation and decreased in obesity in BAT. Inverse correlations of H19 with BMI were also observed in humans. H19 overexpression promoted, while silencing of H19 impaired adipogenesis, oxidative metabolism and mitochondrial respiration in brown but not white adipocytes. In vivo, H19 overexpression protected against DIO, improved insulin sensitivity and mitochondrial biogenesis, whereas fat H19 loss sensitized towards HFD weight gains. Strikingly, paternally expressed genes (PEG) were largely absent from BAT and we demonstrated that H19 recruits PEG-inactivating H19-MBD1 complexes and acts as BAT-selective PEG gatekeeper. This has implications for our understanding how monoallelic gene expression affects metabolism in rodents and, potentially, humans.
Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel
Authors: Li Binsen , Ge Peng , Murray Kevin A. , Sheth Phorum , Zhang Meng , Nair Gayatri , Sawaya Michael R. , Shin Woo Shik , Boyer David R. , Ye Shulin , Eisenberg David S. , Zhou Z. Hong , Jiang Lin
Published: August 2018

α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 Å resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.
Drought reduces blue-water fluxes more strongly than green-water fluxes in Europe
Authors: Orth René , Destouni Georgia
Published: August 2018

Drought comprehensively affects different interlinked aspects of the terrestrial water cycle, which have so far been mostly investigated without direct comparison. Resolving the partitioning of water deficit during drought into blue-water runoff and green-water evapotranspiration fluxes is critical, as anomalies in these fluxes threaten different associated societal sectors and ecosystems. Here, we analyze the propagation of drought-inducing precipitation deficits through soil moisture reductions to their impacts on blue and green-water fluxes by use of comprehensive multi-decadal data from > 400 near-natural catchments along a steep climate gradient across Europe. We show that soil-moisture drought reduces runoff stronger and faster than it reduces evapotranspiration over the entire continent. While runoff responds within weeks, evapotranspiration can be unaffected for months. Understanding these drought-impact pathways across blue and green-water fluxes and geospheres is essential for ensuring food and water security, and developing early-warning and adaptation systems in support of society and ecosystems.
Tree rings reveal globally coherent signature of cosmogenic radiocarbon events in 774 and 993 CE
Authors: Büntgen Ulf , Wacker Lukas , Galván J. Diego , Arnold Stephanie , Arseneault Dominique , Baillie Michael , Beer Jürg , Bernabei Mauro , Bleicher Niels , Boswijk Gretel , Bräuning Achim , Carrer Marco , Ljungqvist Fredrik Charpentier , Cherubini Paolo , Christl Marcus , Christie Duncan A. , Clark Peter W. , Cook Edward R. , D’Arrigo Rosanne , Davi Nicole , Eggertsson Ólafur , Esper Jan , Fowler Anthony M. , Gedalof Ze’ev , Gennaretti Fabio , Grießinger Jussi , Grissino-Mayer Henri , Grudd Håkan , Gunnarson Björn E. , Hantemirov Rashit , Herzig Franz , Hessl Amy , Heussner Karl-Uwe , Jull A. J. Timothy , Kukarskih Vladimir , Kirdyanov Alexander , Kolář Tomáš , Krusic Paul J. , Kyncl Tomáš , Lara Antonio , LeQuesne Carlos , Linderholm Hans W. , Loader Neil J. , Luckman Brian , Miyake Fusa , Myglan Vladimir S. , Nicolussi Kurt , Oppenheimer Clive , Palmer Jonathan , Panyushkina Irina , Pederson Neil , Rybníček Michal , Schweingruber Fritz H. , Seim Andrea , Sigl Michael , Churakova Olga , Speer James H. , Synal Hans-Arno , Tegel Willy , Treydte Kerstin , Villalba Ricardo , Wiles Greg , Wilson Rob , Winship Lawrence J. , Wunder Jan , Yang Bao , Young Giles H. F.
Published: August 2018

Though tree-ring chronologies are annually resolved, their dating has never been independently validated at the global scale. Moreover, it is unknown if atmospheric radiocarbon enrichment events of cosmogenic origin leave spatiotemporally consistent fingerprints. Here we measure the 14C content in 484 individual tree rings formed in the periods 770–780 and 990–1000 CE. Distinct 14C excursions starting in the boreal summer of 774 and the boreal spring of 993 ensure the precise dating of 44 tree-ring records from five continents. We also identify a meridional decline of 11-year mean atmospheric radiocarbon concentrations across both hemispheres. Corroborated by historical eye-witness accounts of red auroras, our results suggest a global exposure to strong solar proton radiation. To improve understanding of the return frequency and intensity of past cosmic events, which is particularly important for assessing the potential threat of space weather on our society, further annually resolved 14C measurements are needed.
microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions
Authors: Paraskevopoulou Maria D. , Karagkouni Dimitra , Vlachos Ioannis S. , Tastsoglou Spyros , Hatzigeorgiou Artemis G.
Published: August 2018

Argonaute crosslinking and immunoprecipitation (CLIP) experiments are the most widely used high-throughput methodologies for miRNA targetome characterization. The analysis of Photoactivatable Ribonucleoside-Enhanced (PAR) CLIP methodology focuses on sequence clusters containing T-to-C conversions. Here, we demonstrate for the first time that the non-T-to-C clusters, frequently observed in PAR-CLIP experiments, exhibit functional miRNA-binding events and strong RNA accessibility. This discovery is based on the analysis of an extensive compendium of bona fide miRNA-binding events, and is further supported by numerous miRNA perturbation experiments and structural sequencing data. The incorporation of these previously neglected clusters yields an average of 14% increase in miRNA-target interactions per PAR-CLIP library. Our findings are integrated in microCLIP (www.microrna.gr/microCLIP), a cutting-edge framework that combines deep learning classifiers under a super learning scheme. The increased performance of microCLIP in CLIP-Seq-guided detection of miRNA interactions, uncovers previously elusive regulatory events and miRNA-controlled pathways.
Dynamic capillary assembly of colloids at interfaces with 10,000g accelerations
Authors: Huerre Axel , De Corato Marco , Garbin Valeria
Published: August 2018

High-rate deformation of soft matter is an emerging area central to our understanding of far-from-equilibrium phenomena during shock, fracture, and phase change. Monolayers of colloidal particles are a convenient two-dimensional model system to visualise emergent behaviours in soft matter, but previous studies have been limited to slow deformations. Here we probe and visualise the evolution of a monolayer of colloids confined at a bubble surface during high-rate deformation driven by ultrasound. We observe the emergence of a transient network of strings, and use discrete particle simulations to show that it is caused by a delicate interplay of dynamic capillarity and hydrodynamic interactions between particles oscillating at high frequency. Remarkably for a colloidal system, we find evidence of inertial effects, caused by accelerations approaching 10,000g. These results also suggest that extreme deformation of soft matter offers new opportunities for pattern formation and dynamic self-assembly.
Role of dimensional crossover on spin-orbit torque efficiency in magnetic insulator thin films
Authors: Shao Qiming , Tang Chi , Yu Guoqiang , Navabi Aryan , Wu Hao , He Congli , Li Junxue , Upadhyaya Pramey , Zhang Peng , Razavi Seyed Armin , He Qing Lin , Liu Yawen , Yang Pei , Kim Se Kwon , Zheng Cheng , Liu Yizhou , Pan Lei , Lake Roger K. , Han Xiufeng , Tserkovnyak Yaroslav , Shi Jing , Wang Kang L.
Published: August 2018

Magnetic insulators (MIs) attract tremendous interest for spintronic applications due to low Gilbert damping and the absence of Ohmic loss. Spin-orbit torques (SOTs) on MIs are more intriguing than magnetic metals since SOTs cannot be transferred to MIs through direct injection of electron spins. Understanding of SOTs on MIs remains elusive, especially how SOTs scale with the MI film thickness. Here, we observe the critical role of dimensionality on the SOT efficiency by studying the MI layer thickness-dependent SOT efficiency in tungsten/thulium iron garnet (W/TmIG) bilayers. We show that the TmIG thin film evolves from two-dimensional to three-dimensional magnetic phase transitions as the thickness increases. We report the significant enhancement of the measured SOT efficiency as the TmIG thickness increases, which is attributed to the increase of the magnetic moment density. We demonstrate the current-induced SOT switching in the W/TmIG bilayers with a TmIG thickness up to 15 nm.
Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses
Authors: Li Qiuhui , Deng Qu , Chao Hsueh-Ping , Liu Xin , Lu Yue , Lin Kevin , Liu Bigang , Tang Gregory W. , Zhang Dingxiao , Tracz Amanda , Jeter Collene , Rycaj Kiera , Calhoun-Davis Tammy , Huang Jiaoti , Rubin Mark A. , Beltran Himisha , Shen Jianjun , Chatta Gurkamal , Puzanov Igor , Mohler James L. , Wang Jianmin , Zhao Ruizhe , Kirk Jason , Chen Xin , Tang Dean G.
Published: August 2018

Expression of androgen receptor (AR) in prostate cancer (PCa) is heterogeneous but the functional significance of AR heterogeneity remains unclear. Screening ~200 castration-resistant PCa (CRPC) cores and whole-mount sections (from 89 patients) reveals 3 AR expression patterns: nuclear (nuc-AR), mixed nuclear/cytoplasmic (nuc/cyto-AR), and low/no expression (AR−/lo). Xenograft modeling demonstrates that AR+ CRPC is enzalutamide-sensitive but AR−/lo CRPC is resistant. Genome editing-derived AR+ and AR-knockout LNCaP cell clones exhibit distinct biological and tumorigenic properties and contrasting responses to enzalutamide. RNA-Seq and biochemical analyses, coupled with experimental combinatorial therapy, identify BCL-2 as a critical therapeutic target and provide proof-of-concept therapeutic regimens for both AR+/hi and AR−/lo CRPC. Our study links AR expression heterogeneity to distinct castration/enzalutamide responses and has important implications in understanding the cellular basis of prostate tumor responses to AR-targeting therapies and in facilitating development of novel therapeutics to target AR−/lo PCa cells/clones.
Quantum nondemolition measurement of mechanical motion quanta
Authors: Dellantonio Luca , Kyriienko Oleksandr , Marquardt Florian , Sørensen Anders S.
Published: August 2018

The fields of optomechanics and electromechanics have facilitated numerous advances in the areas of precision measurement and sensing, ultimately driving the studies of mechanical systems into the quantum regime. To date, however, the quantization of the mechanical motion and the associated quantum jumps between phonon states remains elusive. For optomechanical systems, the coupling to the environment was shown to make the detection of the mechanical mode occupation difficult, typically requiring the single-photon strong-coupling regime. Here, we propose and analyse an electromechanical setup, which allows us to overcome this limitation and resolve the energy levels of a mechanical oscillator. We found that the heating of the membrane, caused by the interaction with the environment and unwanted couplings, can be suppressed for carefully designed electromechanical systems. The results suggest that phonon number measurement is within reach for modern electromechanical setups.
Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas
Authors: Park Hae-Young Lopilly , Kim Jie Hyun , Park Chan Kee
Published: August 2018

Diabetes mellitus and glaucoma are the two major causes of selective retinal ganglion cell (RGC) death. To determine the relationship between autophagy and RGC death, we compared autophagy and the related molecular pathways in diabetic and glaucomatous retinas and examined their effect on RGC survival. Biochemical analysis of microtubule-associated protein light chain 3 (LC3)-II and beclin-1 were observed. To determine the pathways involved in autophagy induction, adenosine monophosphate-activated protein kinase (AMPK) and the mechanistic target of rapamycin (mTOR) were also explored. Beclin-1 and the LC3B-II to LC3B-I ratio significantly elevated at 4 and 8 weeks after glaucoma induction; however, only a slight increase was apparent in the diabetic retina. Significant upregulation of phosphorylated AMPK and downregulation of phosphorylated mTOR was evident in the diabetic retina. After autophagy was inhibited with 3-methyladenine (3-MA), apoptosis of RGCs was significantly increased in the diabetic retinas. However, 3-MA inhibition of autophagy decreased the apoptosis of RGCs in glaucomatous retinas. Therefore, our results suggest that RGC death is differentially regulated by autophagy and that the pathways involved differ depending on the triggering injury.
Comments on two recent publications on GM maize and Roundup
Authors: Eriksson Dennis , Ammann Klaus , Chassy Bruce , Chawade Aakash
Published: August 2018

Two -omics studies on genetically modified maize and Roundup-fed rats, recently published in the journal Scientific Reports, contain serious flaws in the experimental design, methodology and interpretation of results, which we point out here. The use of -omics technologies are of increasing importance in research, however we argue for a cautious approach to the potential application in food safety assessments as these exceptionally sensitive and complex methods require a thorough and detailed evaluation of the biological significance of obtained results. Arising from: Mesnage et al. Sci Rep 7:39328 (2017), Mesnage et al. Sci Rep 6:37855 (2016).
Characterization of lasR-deficient clinical isolates of Pseudomonas aeruginosa
Authors: Wang Yao , Gao Leiqiong , Rao Xiancai , Wang Jing , Yu Hua , Jiang Junru , Zhou Wei , Wang Jin , Xiao Yonghong , Li Mengwen , Zhang Yan , Zhang Kebin , Shen Li , Hua Ziyu
Published: August 2018

Pseudomonas aeruginosa is a prevalent opportunistic pathogen that causes fatal infections in immunocompromised individuals. Quorum sensing (QS) is a cell-to-cell communication process that controls virulence gene expression and biofilm formation in P. aeruginosa. Here, the QS systems and the relevant virulence traits in clinical P. aeruginosa isolates were characterized. Eleven out of the ninety-four P. aeruginosa isolates exhibited a biofilm-deficient phenotype. Two biofilm-deficient isolates, one from blood and the one from pleural effusion, appeared to carry a same mutation in lasR. These two isolates differed in the ability to produce QS-regulated virulence factors, but contained the same functionally deficient LasR with the truncated C-terminal domains and belonged to the same multilocus sequence type (ST227). Chromosomal lasR complementation in these lasR mutants verified that lasR inactivation was the sole cause of las deficiency. LasR was not absolutely required for rhl signal in these lasR mutants, suggesting the presence of lasR-independent QS systems. We provided evidence that the virulence gene expression are not regulated in the same manner in these isolates. These results support the hypothesis that conventional QS hierarchy can be smashed by naturally occurring lasR mutation in clinical P. aeruginosa isolates and that complex QS hierarchy may play a role in maintaining infection of this opportunistic pathogen.
Induction chemotherapy followed by concurrent chemoradiotherapy is benefit for advanced stage nasopharyngeal carcinoma with different nonkeratinizing carcinoma subtypes
Authors: Zang Jian , Li Chen , Xu Man , Xu Wanni , Kang Xiaowei , Wang Jianhua , Luo Shanquan , Shi Mei
Published: August 2018

Given the potentially distinctive histological variations in northwest of China, the aim of current study was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients with different histological types. A total of 301 patients were included in this study. Patients were classified in two cohorts according to the 2005 WHO World Health Organization histological classification: WHO type IIa group and WHO type IIb group. The Kaplan-Meier method was used to detect the efficacy between IC + CCRT and CCRT in two WHO types cohorts. Propensity score matching method was adopted to balance the baseline covariate and eliminate potential selection bias. On propensity matched analyses, IC + CCRT was found to produce better 3-year DMFS and OS than CCRT in WHO type IIa cohort (DMFS, 76.2% vs. 42.2%, p = 0.029; OS, 78.3% vs. 65.5%, p = 0.027). For WHO type IIb cohort, IC + CCRT was associated with a better 3-year OS (87.4% vs. 77.9%, p = 0.029) and a trend of better 3-year DMFS (85.9% vs. 76%, p = 0.162) compared with CCRT. IC + CCRT was benefit for advanced stage nasopharyngeal carcinoma with different nonkeratinizing carcinoma subtypes.
Estimating regional flood discharge during Palaeocene-Eocene global warming
Authors: Chen Chen , Guerit Laure , Foreman Brady Z. , Hassenruck-Gudipati Hima J. , Adatte Thierry , Honegger Louis , Perret Marc , Sluijs Appy , Castelltort Sébastien
Published: August 2018

Among the most urgent challenges in future climate change scenarios is accurately predicting the magnitude to which precipitation extremes will intensify. Analogous changes have been reported for an episode of millennial-scale 5 °C warming, termed the Palaeocene-Eocene Thermal Maximum (PETM; 56 Ma), providing independent constraints on hydrological response to global warming. However, quantifying hydrologic extremes during geologic global warming analogs has proven difficult. Here we show that water discharge increased by at least 1.35 and potentially up to 14 times during the early phase of the PETM in northern Spain. We base these estimates on analyses of channel dimensions, sediment grain size, and palaeochannel gradients across the early PETM, which is regionally marked by an abrupt transition from overbank palaeosol deposits to conglomeratic fluvial sequences. We infer that extreme floods and channel mobility quickly denuded surrounding soil-mantled landscapes, plausibly enhanced by regional vegetation decline, and exported enormous quantities of terrigenous material towards the ocean. These results support hypotheses that extreme rainfall events and associated risks of flooding increase with global warming at similar, but potentially at much higher, magnitudes than currently predicted.
Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens
Authors: Deblais Loïc , Helmy Yosra A. , Kathayat Dipak , Huang Huang-chi , Miller Sally A. , Rajashekara Gireesh
Published: August 2018

The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobial-resistant isolates and the limited effects of current control methods. Advanced chemical technologies have made accessible a wide range of uncharacterized small molecules (SMs) with encouraging chemical properties for antimicrobial treatment. Of the 4,182 SMs screened in vitro, four cidal SMs were effective at 10 µM and higher against several serotypes, antibiotic-resistant, and biofilm embedded Salmonella enterica subsp. enterica serotype Typhimurium by altering cell membrane integrity. The four SMs displayed synergistic effects with ciprofloxacin, meropenem and cefeprime against Salmonella. Further, the SMs were not pernicious to most eukaryotic cells at 200 μM and cleared internalized Salmonella in infected Caco-2, HD11, and THP-1 cells at 6.25 µM and higher. The SMs also increased the longevity of Salmonella-infected Galleria mellonella larvae and reduced the population of internalized Salmonella Typhimurium. Two of the SMs (SM4 and SM5) also reduced S. Typhimurium load in infected chicken ceca as well as its systemic translocation into other tissues, with minimal impact on the cecal microbiota. This study demonstrated that SMs are a viable source of potential antimicrobials applicable in food animal production against Salmonella.
DES-Mutation: System for Exploring Links of Mutations and Diseases
Authors: Kordopati Vasiliki , Salhi Adil , Razali Rozaimi , Radovanovic Aleksandar , Tifratene Faroug , Uludag Mahmut , Li Yu , Bokhari Ameerah , AlSaieedi Ahdab , Bin Raies Arwa , Van Neste Christophe , Essack Magbubah , Bajic Vladimir B.
Published: August 2018

During cellular division DNA replicates and this process is the basis for passing genetic information to the next generation. However, the DNA copy process sometimes produces a copy that is not perfect, that is, one with mutations. The collection of all such mutations in the DNA copy of an organism makes it unique and determines the organism’s phenotype. However, mutations are often the cause of diseases. Thus, it is useful to have the capability to explore links between mutations and disease. We approached this problem by analyzing a vast amount of published information linking mutations to disease states. Based on such information, we developed the DES-Mutation knowledgebase which allows for exploration of not only mutation-disease links, but also links between mutations and concepts from 27 topic-specific dictionaries such as human genes/proteins, toxins, pathogens, etc. This allows for a more detailed insight into mutation-disease links and context. On a sample of 600 mutation-disease associations predicted and curated, our system achieves precision of 72.83%. To demonstrate the utility of DES-Mutation, we provide case studies related to known or potentially novel information involving disease mutations. To our knowledge, this is the first mutation-disease knowledgebase dedicated to the exploration of this topic through text-mining and data-mining of different mutation types and their associations with terms from multiple thematic dictionaries.
Publisher Correction: Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease
Authors: van Raaij Sanne , van Swelm Rachel , Bouman Karlijn , Cliteur Maaike , van den Heuvel Marius C. , Pertijs Jeanne , Patel Dominic , Bass Paul , van Goor Harry , Unwin Robert , Srai Surjit Kaila , Swinkels Dorine
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Urinary neopterin levels increase and predict survival during a respiratory outbreak in wild chimpanzees (Taï National Park, Côte d’Ivoire)
Authors: Wu Doris F. , Behringer Verena , Wittig Roman M. , Leendertz Fabian H. , Deschner Tobias
Published: August 2018

Monitoring immune system activation of wild animals has garnered increasing interest within the field of ecological immunology, leading to an urgent need for non-invasive biomarkers measuring these changes. Urinary neopterin, a marker of the cell-mediated immune response, is validated as an immune-related biomarker in captive and laboratory animals. However, wild animals naturally host higher and chronic pathogen loads. Therefore, detection and quantification of additional infections via neopterin might not be possible against the background of a chronically challenged immune system. To assess the suitability of urinary neopterin in wild animals, we measured neopterin corrected for specific gravity with an enzyme immunoassay in 185 samples collected before, during and after a respiratory disease outbreak in 28 individuals from a group of wild chimpanzees (Taï National Park, Côte d’Ivoire). Urinary neopterin levels were significantly higher during periods when individuals showed respiratory symptoms versus before and after the outbreak. Furthermore, urinary neopterin levels were significantly higher in individuals that died, with higher levels already apparent before the outbreak, suggesting individuals may have an already activated immune system. Measuring urinary neopterin levels, with other biomarkers of energetic condition, stress challenges, and reproduction will contribute towards a deeper understanding of life-history trade-offs in wild animals.
Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor
Authors: Dutton Luke C. , Dudhia Jayesh , Catchpole Brian , Hodgkiss-Geere Hannah , Werling Dirk , Connolly David J.
Published: August 2018

Cardiosphere-derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2.
The contribution of hormone sensitive lipase to adipose tissue lipolysis and its regulation by insulin in periparturient dairy cows
Authors: De Koster Jenne , Nelli Rahul K. , Strieder-Barboza Clarissa , de Souza Jonas , Lock Adam L. , Contreras G. Andres
Published: August 2018

Hormone sensitive lipase (HSL) activation is part of the metabolic adaptations to the negative energy balance common to the mammalian periparturient period. This study determined HSL contribution to adipose tissue (AT) lipolysis and how insulin regulates its activity in periparturient dairy cows. Subcutaneous AT (SCAT) samples were collected at 11 d prepartum (dry) and 11 (fresh) and 24 d (lactation) postpartum. Basal and stimulated lipolysis (ISO) responses were determined using explant cultures. HSL contribution to lipolysis was assessed using an HSL inhibitor (CAY). Basal lipolysis was higher in SCAT at dry compared with fresh. CAY inhibited basal lipolysis negligibly at dry, but at fresh and lactation it reduced basal lipolysis by 36.1 ± 4.51% and 43.1 ± 4.83%, respectively. Insulin inhibited lipolysis more pronouncedly in dry compared to fresh. Results demonstrate that HSL contribution to basal lipolysis is negligible prepartum. However, HSL is a major driver of SCAT lipolytic responses postpartum. Lower basal lipolysis postpartum suggests that reduced lipogenesis is an important contributor to fatty acid release from SCAT. Loss of adipocyte sensitivity to the antilipolytic action of insulin develops in the early lactation period and supports a state of insulin resistance in AT of cows during the first month postpartum.
Prediction of Gestational Diabetes Mellitus and Pre-diabetes 5 Years Postpartum using 75 g Oral Glucose Tolerance Test at 14–16 Weeks’ Gestation
Authors: Lekva Tove , Godang Kristin , Michelsen Annika E. , Qvigstad Elisabeth , Normann Kjersti Ringvoll , Norwitz Errol R. , Aukrust Pål , Henriksen Tore , Bollerslev Jens , Roland Marie Cecilie Paasche , Ueland Thor
Published: August 2018

Early detection and treatment of women at risk for gestational diabetes mellitus (GDM) could improve perinatal and long-term outcomes in GDM women and their offspring. We explored if a 75 g oral glucose tolerance test (OGTT) at 14–16 weeks of gestation could identify women who will (1) develop GDM or give birth to large-for-gestational-age (LGA) babies in 1031 pregnant women from the STORK study using different diagnostic criteria (WHO1999, IADPSG2010, WHO2013, NORWAY2017) and (2) develop pre-diabetes 5 years postpartum focusing on first trimester β-cell function in a separate study of 300 women from the STORK cohort. The sensitivity of the 14–16 week OGTT to identify women who would develop GDM or have LGA babies was low, and we could not identify alternative cut-offs to exclude women not at risk or identify women that could benefit from early intervention. First trimester β-cell function was a stronger determinant than third trimester β-cell function of predicting maternal pre-diabetes. In conclusion, in our normal low-risk population, the 75 g OGTT at 14–16 weeks is insufficient to identify candidates for early treatment of GDM or identify women not likely to develop GDM or have LGA babies. First trimester β-cell function may predict pre-diabetes 5 years postpartum.
Human susceptibility to social influence and its neural correlates are related to perceived vulnerability to extrinsic morbidity risks
Authors: Jacquet Pierre O. , Wyart Valentin , Desantis Andrea , Hsu Yi-Fang , Granjon Lionel , Sergent Claire , Waszak Florian
Published: August 2018

Humans considerably vary in the degree to which they rely on their peers to make decisions. Why? Theoretical models predict that environmental risks shift the cost-benefit trade-off associated with the exploitation of others’ behaviours (public information), yet this idea has received little empirical support. Using computational analyses of behaviour and multivariate decoding of electroencephalographic activity, we test the hypothesis that perceived vulnerability to extrinsic morbidity risks impacts susceptibility to social influence, and investigate whether and how this covariation is reflected in the brain. Data collected from 261 participants tested online revealed that perceived vulnerability to extrinsic morbidity risks is positively associated with susceptibility to follow peers’ opinion in the context of a standard face evaluation task. We found similar results on 17 participants tested in the laboratory, and showed that the sensitivity of EEG signals to public information correlates with the participants’ degree of vulnerability. We further demonstrated that the combination of perceived vulnerability to extrinsic morbidity with decoding sensitivities better predicted social influence scores than each variable taken in isolation. These findings suggest that susceptibility to social influence is partly calibrated by perceived environmental risks, possibly via a tuning of neural mechanisms involved in the processing of public information.