bluuebunny/crossref_metadata_2025 huggingface dataset:
An overview of the epidemiology of notifiable infectious diseases in Australia, 1991–2011
Authors: GIBNEY K. B. , CHENG A. C. , HALL R. , LEDER K.
Published: June 2016

We reviewed the first 21 years (1991–2011) of Australia's National Notifiable Diseases Surveillance System (NNDSS). All nationally notified diseases (except HIV/AIDS and Creutzfeldt–Jakob disease) were analysed by disease group (n= 8), jurisdiction (six states and two territories), Indigenous status, age group and notification year. In total, 2 421 134 cases were analysed. The 10 diseases with highest notification incidence (chlamydial infection, campylobacteriosis, varicella zoster, hepatitis C, influenza, pertussis, salmonellosis, hepatitis B, gonococcal infection, and Ross River virus infection) comprised 88% of all notifications. Annual notification incidence was 591 cases/100 000, highest in the Northern Territory (2598/100 000) and in children aged <5 years (698/100 000). A total of 8·4% of cases were Indigenous Australians. Notification incidence increased by 6·4% per year (12% for sexually transmissible infections and 15% for vaccine-preventable diseases). The number of notifiable diseases also increased from 37 to 65. The number and incidence of notifications increased throughout the study period, partly due to addition of diseases to the NNDSS and increasing availability of sensitive diagnostic tests. The most commonly notified diseases require a range of public health responses addressing high-risk sexual and drug-use behaviours, food safety and immunization. Our results highlight populations with higher notification incidence that might require tailored public health interventions.
Gender disparities in mortality from infectious diseases in Serbia, 1991–2014: a time of civil wars and global crisis
Authors: ILIC M. , ILIC I.
Published: June 2016

Infectious diseases remain one of the leading causes of death worldwide. The aim of this descriptive epidemiological study was to analyse the trends in mortality from infectious diseases in Serbia (excluding the Autonomous Province of Kosovo & Metohia) from 1991 to 2014 using joinpoint regression analysis. The mortality rates from infectious diseases were found to have increased markedly from 1991 to 1994 (+12·4% per year), followed by a significant decline from 1994 to 2009 (–4·6% per year) and then another increase from 2009 to 2014 (+4·3% per year). Throughout the study period, mortality rates were consistently higher in men than in women. Although a substantial decline was observed for young people of both sexes, no consistent pattern was evident for the middle-aged nor the elderly. Since 1991, septicaemia has emerged as a leading cause of infectious disease mortality, particularly in older men. The Yugoslav civil wars in the 1990s and the global financial crisis in 2008 corresponded with changes in the trends in mortality from infectious diseases in Serbia, with the elderly showing particular vulnerability during those time periods. Data presented in this study might be useful to improve control of infectious diseases in Serbia.
Composable scheduler activations for Haskell
Authors: SIVARAMAKRISHNAN K. C. , HARRIS TIM , MARLOW SIMON , PEYTON JONES SIMON
Published: June 2016

The runtime for a modern, concurrent, garbage collected language like Java or Haskell is like an operating system: sophisticated, complex, performant, but alas very hard to change. If more of the runtime system were in the high-level language, it would be far more modular and malleable. In this paper, we describe a novel concurrency substrate design for the Glasgow Haskell Compiler that allows multicore schedulers for concurrent and parallel Haskell programs to be safely and modularly described as libraries in Haskell. The approach relies on abstracting the interface to the user-implemented schedulers through scheduler activations, together with the use of Software Transactional Memory to promote safety in a multicore context.
Physician-Assisted Death in Canada
Authors: BROWNE ALISTER , RUSSELL J. S.
Published: June 2016

The Criminal Code of Canada prohibits persons from aiding or abetting suicide and consenting to have death inflicted on them. Together, these provisions have prohibited physicians from assisting patients to die. On February 6, 2015, the Supreme Court of Canada declared void these provisions insofar as they “prohibit physician-assisted death for a competent adult person who (1) clearly consents to the termination of life and (2) has a grievous and irremediable medical condition (including an illness, disease or disability) that causes enduring suffering that is intolerable to the individual in the circumstances of his or her condition.” This declaration of invalidity was scheduled to take effect one year (later extended by six months) after the ruling, to give the government time to put legislation in place. We trace the history of this decision, discuss how it has forever changed the debate on physician-assisted dying, and identify the issues that must be resolved to write the legislation. Of special importance here are the topics of access, safeguards, and conscientious objection.
Euthanasia for Detainees in Belgium
Authors: DEVOLDER KATRIEN
Published: June 2016

In 2011, Frank Van Den Bleeken became the first detainee to request euthanasia under Belgium’s Euthanasia Act of 2002. This article investigates whether it would be lawful and morally permissible for a doctor to accede to this request. Though Van Den Bleeken has not been held accountable for the crimes he committed, he has been detained in an ordinary prison, without appropriate psychiatric care, for more than 30 years. It is first established that Van Den Bleeken’s euthanasia request plausibly meets the relevant conditions of the Euthanasia Act and that, consequently, a doctor could lawfully fulfill it. Next, it is argued that autonomy-based reasons for euthanizing him outweigh complicity-based reasons against doing so, and that, therefore, it is also morally permissible for a doctor to carry out the euthanasia request.
Communicating Concerns
Authors: BUIJSEN MARTIN
Published: June 2016

The Dutch Euthanasia Act seems to be set in stone. Since it took effect in 2002, it has not seen any significant amendments. Recent developments, however, indicate that a major component of the act—the review procedure—is due for revision. The review practice of the regional euthanasia review committees—responsible for applying and interpreting the law—now also extends to instances of euthanasia and assisted suicide for special categories of patients: psychiatric patients, patients with early-stage dementia, and patients whose suffering is derived from a combination of medical and existential causes. In this article, it is argued that a reconsideration of the review practice for these new cases is necessary primarily because review committees lack the legitimacy needed for the development of policies with such a large impact on society.
The Measles and Free Riders
Authors: BROWNE KATHARINE
Published: June 2016

This article takes up a game-theoretic perspective on California’s recently passed bill (SB 277) that closes all nonmedical exemptions for school-mandated vaccination. Such a perspective characterizes parental decisions to vaccinate their children as a collective action problem and reveals the presence of an incentive to free ride—to enjoy the benefits of others’ efforts to vaccinate their children without vaccinating one’s own. This article defends California’s legislation as a reasonable means of overcoming the free rider problem and of ensuring that the burdens of vaccination are shared equally.
The Role of Physicians in State-Sponsored Corporal Punishment
Authors: MUAYGIL RUAIM
Published: June 2016

The question of whether there is justification for physicians to participate in state-sanctioned corporal punishment has prompted long and heated debates around the world. Several recent and high-profile sentences requiring physician assistance have brought the conversation to Saudi Arabia. Whether a physician is asked to participate actively or to assess prisoners’ ability to withstand this form of punishment, can there be an ethical justification for medical training and skills being put toward these purposes? The aim of this article is to examine aspects of Islamic law along with the different professional and religious obligations of Saudi Arabian physicians, and how these elements may inform the debate.
Commentary: The Broader Context of Long-Term Care Ethics
Authors: Lesandrini Jason , O’Connell Carol
Published: June 2016

Ethical issues in long-term care settings, although having received attention in the literature, have not in our opinion received the appropriate level they require. Thus, we applaud the Cambridge Quarterly for publishing this case. We can attest to the significance of ethical issues arising in long-term care facilities, as Mr. Hope’s case is all too familiar to those practicing in these settings. What is unique about this case is that an actual ethics consult was made in a long-term care setting. We have seen very little in the published literature on the use of ethics structures in long-term care populations. Our experience is that these healthcare settings are ripe for ethical concerns and that providers, patients, families, and staff need/desire ethics resources to actively and preventively address ethical concerns. The popular press has begun to recognize the ethical issues involved in long-term care settings and the need for ethics structures. Recently, in California a nurse refused to initiate CPR for an elderly patient in a senior residence. In that case, the nurse was quoted as saying that the facility had a policy that nurses were not to start CPR for elderly patients.1 Although this case is not exactly the same as that of Mr. Hope, it highlights the need for developing robust ethics program infrastructures in long-term care settings that work toward addressing ethical issues through policy, education, and active consultation.
Impact of Personality on Cognitive Aging: A Prospective Cohort Study
Authors: Caselli Richard J. , Dueck Amylou C. , Locke Dona E.C. , Henslin Bruce R. , Johnson Travis A. , Woodruff Bryan K. , Hoffman-Snyder Charlene , Geda Yonas E.
Published: June 2016

Objectives: The aim of this study was to assess the association between personality factors and age-related longitudinal cognitive performance, and explore interactions of stress-proneness with apolipoprotein E (APOE) ɛ4, a prevalent risk factor for Alzheimer’s disease (AD). Methods: A total of 510 neuropsychiatrically healthy residents of Maricopa County recruited through media ads (mean age 57.6±10.6 years; 70% women; mean education 15.8±2.4 years; 213 APOE ɛ4 carriers) had neuropsychological testing every 2 years (mean duration follow-up 9.1±4.4 years), and the complete Neuroticism Extraversion Openness Personality Inventory-Revised. Several tests were administered within each of the following cognitive domains: memory, executive skills, language, visuospatial skills, and general cognition. Primary effects on cognitive trajectories and APOE ɛ4 interactions were ascertained with quadratic models. Results: With personality factors treated as continuous variables, Neuroticism was associated with greater decline, and Conscientiousness associated with reduced decline consistently across tests in memory and executive domains. With personality factors trichotomized, the associations of Neuroticism and Conscientiousness were again highly consistent across tests within memory and to a lesser degree executive domains. While age-related memory decline was greater in APOE ɛ4 carriers as a group than ɛ4 noncarriers, verbal memory decline was mitigated in ɛ4 carriers with higher Conscientiousness, and visuospatial perception and memory decline was mitigated in ɛ4 carriers with higher Openness. Conclusions: Neuroticism and Conscientiousness were associated with changes in longitudinal performances on tests sensitive to memory and executive skills. APOE interactions were less consistent. Our findings are consistent with previous studies that have suggested that personality factors, particularly Neuroticism and Conscientiousness are associated with cognitive aging patterns. (JINS, 2016, 22, 765–776)
Associations between reported intakes of carotenoid-rich foods and concentrations of carotenoids in plasma: a validation study of a web-based food recall for children and adolescents
Authors: Medin Anine Christine , Carlsen Monica Hauger , Andersen Lene Frost
Published: June 2016

Objective

To validate estimated intakes of carotenoid-rich foods from a web-based food recall (WebFR) using carotenoids in blood as an objective reference method.

Design

Cross-sectional validation study using carotenoids in plasma to evaluate estimated intakes of selected carotenoid-rich foods. Participants recorded their food intake in the WebFR and plasma concentrations of β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin were measured.

Setting

Schools and homes of families in a suburb of the capital of Norway.

Subjects

A total of 261 participants in the age groups 8–9 and 12–14 years.

Results

Spearman’s rank correlation coefficients ranged from 0·30 to 0·44, and cross-classification showed that 71·6–76·6 % of the participants were correctly classified, when comparing the reported intakes of carotenoid-rich foods and concentrations of the corresponding carotenoids in plasma, not including lutein and zeaxanthin.

Conclusions

Correlations were acceptable and cross-classification analyses demonstrated that the WebFR was able to rank participants according to their reported intake of foods rich in α-carotene, β-carotene, β-cryptoxanthin and lycopene. The WebFR is a promising tool for dietary assessment among children and adolescents.
Breast leptomeningeal metastasis recurrence presenting as a manic episode
Authors: Reich Michel , Girard Edwina , Le Rhun Emilie
Published: June 2016

Objective:

Leptomeningeal metastasis (LM) is a neurooncological complication of advanced cancer that has a poor prognosis. The incidence of LM is increasing due to advances in neuroimaging. At the same time, the development of new systemic treatments with poor central nervous system penetration has improved outcomes and survival. However, diagnosis of LM remains quite difficult due to clinical polymorphism, inconsistent imaging abnormalities, and the inconsistent presence of neoplastic cells in cerebrospinal fluid. Psychiatric manifestations can blur the neurological frame and confound management of this complication.

Method:

To illustrate these difficulties, we report the case of a patient with no past psychiatric history who presented with a manic episode that was attributed to a recurrence of leptomeningeal metastasis.

Results:

With this case report, we highlight the importance of referring the patient to a psychiatrist or a member of the psychooncology unit when new behavioral disorders present.

Significance of results:

Leptomeningeal metastases can elicit psychiatric consequences. A hypothesis of this diagnosis should be considered for cancer patients who present with sudden or recent profound mental changes during the course of their disease. Oncologists and neurooncologists should be aware of this possibility. Collaboration with a psychooncologist is recommended to better manage this neuropsychiatric pathology.
Dietary intakes and anthropometric measures of Indigenous Australian women and their infants in the Gomeroi gaaynggal cohort
Authors: Ashman A. M. , Collins C. E. , Weatherall L. J. , Keogh L. , Brown L. J. , Rollo M. E. , Smith R. , Rae K. M.
Published: June 2016

Indigenous Australians continue to experience disparities in chronic diseases, many of which have nutrition-related trajectories. Optimal nutrition throughout the lifespan is protective for a number of adverse health outcomes, however little is known about current dietary intakes and related anthropometric outcomes of Indigenous women and their infants. Research is required to identify nutrition issues to target for health promotion activities. The Gomeroi gaaynggal programme is an ongoing, prospective cohort of pregnant Indigenous Australian women and their children. A cross-sectional examination of postnatal dietary intakes and anthropometric outcomes of mothers and children are reported. To date, 73 mother–child dyads have participatedpostpartum. Breastfeeding initiation was 85.9% and median (interquartile range) duration of any breastfeeding was 1.4 (0.5–4.0) months. Infants were introduced to solid foods at 5.0 months (4.0–6.0) and cow’s milk at 12.0 (10.0–13.0) months. At 12 monthspostpartum, 66.7% of women were overweight or obese, 63.7% at 2 years. Compared with recommendations, reported median maternal nutrient intakes from 24-h recall were low in fibre, folate, iodine, calcium, potassium and vitamin D and high in proportions of energy from total and saturated fat. Limitations of this study include a small sample size and incomplete data for the cohort at each time point. Preliminary data from this ongoing cohort of Indigenous Australian women and children suggest that women may need support to optimize nutrient intakes and to attain a healthy body weight for themselves and their children.
Parent-Reported Outcomes Associated With Utilization of a Pediatric Cancer School Consultation Program
Authors: Rubens Sonia L. , Loucas Caitlyn A. , Morris Marybeth , Manley Peter E. , Ullrich Nicole J. , Muriel Anna C. , Guo Dongjing , London Wendy B. , Northman Lisa
Published: June 2016

Childhood survivors of central nervous system (CNS) cancers are at risk for cognitive and physical late effects that can negatively influence their school functioning. Although many hospital-based programs assist in school re-entry for pediatric cancer patients, few address the long-term academic needs of this population. This study examined parent-reported outcomes associated with participation in a hospital-based school liaison program (SLP) to address the long-term needs of survivors of pediatric CNS cancers. Participants included 93 parents (91% mothers, 94% Caucasian) of children enrolled in a hospital-based SLP. Parents completed measures of SLP services received and their perceptions of their own ability to navigate and understand the special education system, including perceived understanding of their children’s learning needs, confidence in their own ability to advocate, belief in being informed of available services, difficulty obtaining school supports, and belief that a child is meeting his or her academic potential. Univariate logistic regressions showed that longer time spent receiving SLP services, having an SLP clinician participate at school meetings, and having an SLP clinician visit a patient’s school were uniquely associated with numerous positive parent-perceived outcomes. Understanding outcomes associated with participation in programs that support collaborations between a child’s home, school, and hospital can inform best practices for pediatric cancer survivors and the multiple systems of care involved in their development.
Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks
Authors: Rendeiro André F. , Schmidl Christian , Strefford Jonathan C. , Walewska Renata , Davis Zadie , Farlik Matthias , Oscier David , Bock Christoph
Published: June 2016

Chronic lymphocytic leukaemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, here we present genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients measured by the ATAC-seq assay. We also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting data set, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status—which distinguishes the two major subtypes of CLL—was accurately predicted by the chromatin profiles and gene regulatory networks inferred for IGHV-mutated versus IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukaemia and demonstrated the feasibility of large-scale chromatin accessibility mapping in cancer cohorts and clinical research.
Dual nature of magnetic dopants and competing trends in topological insulators
Authors: Sessi Paolo , Biswas Rudro R. , Bathon Thomas , Storz Oliver , Wilfert Stefan , Barla Alessandro , Kokh Konstantin A. , Tereshchenko Oleg E. , Fauth Kai , Bode Matthias , Balatsky Alexander V.
Published: June 2016

Topological insulators interacting with magnetic impurities have been reported to host several unconventional effects. These phenomena are described within the framework of gapping Dirac quasiparticles due to broken time-reversal symmetry. However, the overwhelming majority of studies demonstrate the presence of a finite density of states near the Dirac point even once topological insulators become magnetic. Here, we map the response of topological states to magnetic impurities at the atomic scale. We demonstrate that magnetic order and gapless states can coexist. We show how this is the result of the delicate balance between two opposite trends, that is, gap opening and emergence of a Dirac node impurity band, both induced by the magnetic dopants. Our results evidence a more intricate and rich scenario with respect to the once generally assumed, showing how different electronic and magnetic states may be generated and controlled in this fascinating class of materials.
Skin-inspired hydrogel–elastomer hybrids with robust interfaces and functional microstructures
Authors: Yuk Hyunwoo , Zhang Teng , Parada German Alberto , Liu Xinyue , Zhao Xuanhe
Published: June 2016

Inspired by mammalian skins, soft hybrids integrating the merits of elastomers and hydrogels have potential applications in diverse areas including stretchable and bio-integrated electronics, microfluidics, tissue engineering, soft robotics and biomedical devices. However, existing hydrogel–elastomer hybrids have limitations such as weak interfacial bonding, low robustness and difficulties in patterning microstructures. Here, we report a simple yet versatile method to assemble hydrogels and elastomers into hybrids with extremely robust interfaces (interfacial toughness over 1,000 Jm−2) and functional microstructures such as microfluidic channels and electrical circuits. The proposed method is generally applicable to various types of tough hydrogels and diverse commonly used elastomers including polydimethylsiloxane Sylgard 184, polyurethane, latex, VHB and Ecoflex. We further demonstrate applications enabled by the robust and microstructured hydrogel–elastomer hybrids including anti-dehydration hydrogel–elastomer hybrids, stretchable and reactive hydrogel–elastomer microfluidics, and stretchable hydrogel circuit boards patterned on elastomer.
p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming
Authors: Saito Tetsuya , Ichimura Yoshinobu , Taguchi Keiko , Suzuki Takafumi , Mizushima Tsunehiro , Takagi Kenji , Hirose Yuki , Nagahashi Masayuki , Iso Tetsuro , Fukutomi Toshiaki , Ohishi Maki , Endo Keiko , Uemura Takefumi , Nishito Yasumasa , Okuda Shujiro , Obata Miki , Kouno Tsuguka , Imamura Riyo , Tada Yukio , Obata Rika , Yasuda Daisuke , Takahashi Kyoko , Fujimura Tsutomu , Pi Jingbo , Lee Myung-Shik , Ueno Takashi , Ohe Tomoyuki , Mashino Tadahiko , Wakai Toshifumi , Kojima Hirotatsu , Okabe Takayoshi , Nagano Tetsuo , Motohashi Hozumi , Waguri Satoshi , Soga Tomoyoshi , Yamamoto Masayuki , Tanaka Keiji , Komatsu Masaaki
Published: June 2016

p62/Sqstm1 is a multifunctional protein involved in cell survival, growth and death, that is degraded by autophagy. Amplification of the p62/Sqstm1 gene, and aberrant accumulation and phosphorylation of p62/Sqstm1, have been implicated in tumour development. Herein, we reveal the molecular mechanism of p62/Sqstm1-dependent malignant progression, and suggest that molecular targeting of p62/Sqstm1 represents a potential chemotherapeutic approach against hepatocellular carcinoma (HCC). Phosphorylation of p62/Sqstm1 at Ser349 directs glucose to the glucuronate pathway, and glutamine towards glutathione synthesis through activation of the transcription factor Nrf2. These changes provide HCC cells with tolerance to anti-cancer drugs and proliferation potency. Phosphorylated p62/Sqstm1 accumulates in tumour regions positive for hepatitis C virus (HCV). An inhibitor of phosphorylated p62-dependent Nrf2 activation suppresses the proliferation and anticancer agent tolerance of HCC. Our data indicate that this Nrf2 inhibitor could be used to make cancer cells less resistant to anticancer drugs, especially in HCV-positive HCC patients.
PACAP suppresses dry eye signs by stimulating tear secretion
Authors: Nakamachi Tomoya , Ohtaki Hirokazu , Seki Tamotsu , Yofu Sachiko , Kagami Nobuyuki , Hashimoto Hitoshi , Shintani Norihito , Baba Akemichi , Mark Laszlo , Lanekoff Ingela , Kiss Peter , Farkas Jozsef , Reglodi Dora , Shioda Seiji
Published: June 2016

Dry eye syndrome is caused by a reduction in the volume or quality of tears. Here, we show that pituitary adenylate cyclase-activating polypeptide (PACAP)-null mice develop dry eye-like symptoms such as corneal keratinization and tear reduction. PACAP immunoreactivity is co-localized with a neuronal marker, and PACAP receptor (PAC1-R) immunoreactivity is observed in mouse infraorbital lacrimal gland acinar cells. PACAP eye drops stimulate tear secretion and increase cAMP and phosphorylated (p)-protein kinase A levels in the infraorbital lacrimal glands that could be inhibited by pre-treatment with a PAC1-R antagonist or an adenylate cyclase inhibitor. Moreover, these eye drops suppress corneal keratinization in PACAP-null mice. PACAP eye drops increase aquaporin 5 (AQP5) levels in the membrane and pAQP5 levels in the infraorbital lacrimal glands. AQP5 siRNA treatment of the infraorbital lacrimal gland attenuates PACAP-induced tear secretion. Based on these results, PACAP might be clinically useful to treat dry eye disorder.
Correction: Corrigendum: Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3
Authors: Yahara Yasuhito , Takemori Hiroshi , Okada Minoru , Kosai Azuma , Yamashita Akihiro , Kobayashi Tomohito , Fujita Kaori , Itoh Yumi , Nakamura Masahiro , Fuchino Hiroyuki , Kawahara Nobuo , Fukui Naoshi , Watanabe Akira , Kimura Tomoatsu , Tsumaki Noriyuki
Published: June 2016

Nature Communications 7: Article number: 10959 (2016); Published: 24 March 2016; Updated: 27 June 2016 In this Article, there is an error in the labelling of the western blot in Fig. 3f. The labels indicating the presence of pterosin B in each lane should read ‘−++ +’. The correct version of Fig. 3 appears below.
Introducing SEARCHBreast: a virtual resource to facilitate sharing of surplus animal material developed for breast cancer research
Authors: Morrissey Bethny , Holen Ingunn , Chelala Claude , Carter Phil , Jones Louise , Blyth Karen , Speirs Valerie
Published: June 2016

Animals studies have made significant contribution to expanding our knowledge of breast cancer. Often material is leftover and archived. SEARCHBreast provides a platform for collaborative sharing of archived material via a dedicated on-line database whereby users can both share and search available tissue. The SEARCHBreast database has information on over 50 different mouse models, including tissue from PDX models, available to share. With thousands of samples freely available, SEARCHBreast should be the first point of call for any researcher looking for animal material to aid their breast cancer research.
Quantum random number generation
Authors: Ma Xiongfeng , Yuan Xiao , Cao Zhu , Qi Bing , Zhang Zhen
Published: June 2016

Quantum physics can be exploited to generate true random numbers, which have important roles in many applications, especially in cryptography. Genuine randomness from the measurement of a quantum system reveals the inherent nature of quantumness—coherence, an important feature that differentiates quantum mechanics from classical physics. The generation of genuine randomness is generally considered impossible with only classical means. On the basis of the degree of trustworthiness on devices, quantum random number generators (QRNGs) can be grouped into three categories. The first category, practical QRNG, is built on fully trusted and calibrated devices and typically can generate randomness at a high speed by properly modelling the devices. The second category is self-testing QRNG, in which verifiable randomness can be generated without trusting the actual implementation. The third category, semi-self-testing QRNG, is an intermediate category that provides a tradeoff between the trustworthiness on the device and the random number generation speed.
Erratum: Rate-dependent interface capture beyond the coffee-ring effect
Authors: Li Yanan , Yang Qiang , Li Mingzhu , Song Yanlin
Published: June 2016

Scientific Reports 6: Article number: 24628; published online: 19 April 2016; updated: 27 June 2016. An incorrect Supplementary Information file was inadvertently published with this Article. In addition, Supplementary Movies 1–5 were omitted. The correct Supplementary Information and Supplementary Movies now accompany the Article.
Identifying Kinase Substrates via a Heavy ATP Kinase Assay and Quantitative Mass Spectrometry
Authors: Müller André C. , Giambruno Roberto , Weißer Juliane , Májek Peter , Hofer Alexandre , Bigenzahn Johannes W. , Superti-Furga Giulio , Jessen Henning J. , Bennett Keiryn L.
Published: June 2016

Mass spectrometry-based in vitro kinase screens play an essential role in the discovery of kinase substrates, however, many suffer from biological and technical noise or necessitate genetically-altered enzyme-cofactor systems. We describe a method that combines stable γ-[18O2]-ATP with classical in vitro kinase assays within a contemporary quantitative proteomic workflow. Our approach improved detection of known substrates of the non-receptor tyrosine kinase ABL1; and identified potential, new in vitro substrates.
Curcumin protects mice from Staphylococcus aureus pneumonia by interfering with the self-assembly process of α-hemolysin
Authors: Wang Jianfeng , Zhou Xuan , Li Wenhua , Deng Xuming , Deng Yanhong , Niu Xiaodi
Published: June 2016

α-hemolysin (Hla) is a self-assembling extracellular protein secreted as a soluble monomer by most Staphylococcus aureus strains and is an essential virulence factor for the pathogenesis of various S. aureus infections. Here, we show that curcumin (CUR), a natural compound with weak anti-S. aureus activity, can inhibit the hemolysis induced by Hla. Molecular dynamics simulations, free energy calculations and mutagenesis assays were further employed for the Hla-CUR complex to determine the mechanism of such inhibition. The analysis of this combined approach indicated that the direct binding CUR to Hla blocks the conformational transition of Hla from the monomer to the oligomer, leading to an inhibition of Hla hemolytic activity. We also found that the addition of CUR significantly attenuated Hla-mediated injury of human alveolar cell (A549) co-cultured with S. aureus. The in vivo data further demonstrated that treatment with CUR protects mice from pneumonia caused by S. aureus, including methicillin-resistant strains (MRSA). These findings suggest that CUR inhibits the pore-forming activity of Hla through a novel mechanism, which would pave the way for the development of new and more effective antibacterial agents to combat S. aureus pneumonia.
Correction: Corrigendum: Predicting postoperative vomiting among orthopedic patients receiving patient-controlled epidural analgesia using SVM and LR
Authors: Wu Hsin-Yun , Gong Cihun-Siyong Alex , Lin Shih-Pin , Chang Kuang-Yi , Tsou Mei-Yung , Ting Chien-Kun
Published: June 2016

Scientific Reports 6: Article number: 27041; published online: 01 June 2016; updated: 27 June 2016. In this Article, Shih-Pin Lin is incorrectly affiliated with ‘Portable Energy System Group, Green Technology Research Center, College of Engineering, Chang Gung University, Taoyuan County 33302, Taiwan’.
Correction: Corrigendum: Improved Drain Current Saturation and Voltage Gain in Graphene–on–Silicon Field Effect Transistors
Authors: Song Seung Min , Bong Jae Hoon , Hwang Wan Sik , Cho Byung Jin
Published: June 2016

Scientific Reports 6: Article number: 25392; published online: 04 May 2016; updated: 27 June 2016. This Article contains errors in the Acknowledgements section. “This work was supported by research grants from the National Research Foundation (NRF) of Korea (2010-0029132 and 2011-0031638).” should read:
Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls
Authors: Chen Jun , Chia Nicholas , Kalari Krishna R. , Yao Janet Z. , Novotna Martina , Paz Soldan M. Mateo , Luckey David H. , Marietta Eric V. , Jeraldo Patricio R. , Chen Xianfeng , Weinshenker Brian G. , Rodriguez Moses , Kantarci Orhun H. , Nelson Heidi , Murray Joseph A. , Mangalam Ashutosh K.
Published: June 2016

Multiple sclerosis (MS) is an immune-mediated disease, the etiology of which involves both genetic and environmental factors. The exact nature of the environmental factors responsible for predisposition to MS remains elusive; however, it’s hypothesized that gastrointestinal microbiota might play an important role in pathogenesis of MS. Therefore, this study was designed to investigate whether gut microbiota are altered in MS by comparing the fecal microbiota in relapsing remitting MS (RRMS) (n = 31) patients to that of age- and gender-matched healthy controls (n = 36). Phylotype profiles of the gut microbial populations were generated using hypervariable tag sequencing of the V3–V5 region of the 16S ribosomal RNA gene. Detailed fecal microbiome analyses revealed that MS patients had distinct microbial community profile compared to healthy controls. We observed an increased abundance of Psuedomonas, Mycoplana, Haemophilus, Blautia, and Dorea genera in MS patients, whereas control group showed increased abundance of Parabacteroides, Adlercreutzia and Prevotella genera. Thus our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and further study is needed to better understand their role in the etiopathogenesis of MS.
Bactericidal Effects against S. aureus and Physicochemical Properties of Plasma Activated Water stored at different temperatures
Authors: Shen Jin , Tian Ying , Li Yinglong , Ma Ruonan , Zhang Qian , Zhang Jue , Fang Jing
Published: June 2016

Water activated by non-thermal plasma creates an acidified solution containing reactive oxygen and nitrogen species, known as plasma-activated water (PAW). The objective of this study was to investigate the effects of different storage temperatures (25 °C, 4 °C, −20 °C, −80 °C) on bactericidal activities againstS. aureusand physicochemical properties of PAW up to 30 days. Interestingly, PAW stored at −80 °C yielded the best antibacterial activity againstStaphylococcus aureus, 3~4 log reduction over a 30-day period after PAW generation; meanwhile, PAW stored at 25 °C, 4 °C and −20 °C, respectively, yielded 0.2~2 log decrease in cell viability after the same exposure and storage time. These results were verified by scanning electron microscope (SEM). The physicochemical properties of PAW stored at different temperatures were evaluated, including pH, oxidation reduction potential (ORP) and hydrogen peroxide, nitrate, nitrite anion and NO radical levels. These findings suggested that bacterial activity of PAW stored at 25 °C, 4 °C, −20 °C decreased over time and depended on three germicidal factors, specifically ORP, H2O2and NO3−. Moreover, PAW stored at −80 °C retained bactericidal activity, with NO2−contributing to bactericidal ability in association with H2O2. Our findings provide a basis for PAW storage and practical applications in disinfection and food preservation.
Few-layer Phosphorene: An Ideal 2D Material For Tunnel Transistors
Authors: Ameen Tarek A. , Ilatikhameneh Hesameddin , Klimeck Gerhard , Rahman Rajib
Published: June 2016

2D transition metal dichalcogenides (TMDs) have attracted a lot of attention recently for energy-efficient tunneling-field-effect transistor (TFET) applications due to their excellent gate control resulting from their atomically thin dimensions. However, most TMDs have bandgaps (Eg) and effective masses (m*) outside the optimum range needed for high performance. It is shown here that the newly discovered 2D material, few-layer phosphorene, has several properties ideally suited for TFET applications: 1) direct Eg in the optimum range ~1.0–0.4 eV, 2) light transport m* (0.15 m0), 3) anisotropic m* which increases the density of states near the band edges and 4) a high mobility. These properties combine to provide phosphorene TFET outstanding ION ~ 1 mA/um, ON/OFF ratio ~ 106 for a 15 nm channel and 0.5 V supply voltage, thereby significantly outperforming the best TMD-TFETs and CMOS in many aspects such as ON/OFF current ratio and energy-delay products. Furthermore, phosphorene TFETS can scale down to 6 nm channel length and 0.2 V supply voltage within acceptable range in deterioration of the performance metrics. Full-band atomistic quantum transport simulations establish phosphorene TFETs as serious candidates for energy-efficient and scalable replacements of MOSFETs.
3D Stretchable Arch Ribbon Array Fabricated via Grayscale Lithography
Authors: Pang Yu , Shu Yi , Shavezipur Mohammad , Wang Xuefeng , Mohammad Mohammad Ali , Yang Yi , Zhao Haiming , Deng Ningqin , Maboudian Roya , Ren Tian-Ling
Published: June 2016

Microstructures with flexible and stretchable properties display tremendous potential applications including integrated systems, wearable devices and bio-sensor electronics. Hence, it is essential to develop an effective method for fabricating curvilinear and flexural microstructures. Despite significant advances in 2D stretchable inorganic structures, large scale fabrication of unique 3D microstructures at a low cost remains challenging. Here, we demonstrate that the 3D microstructures can be achieved by grayscale lithography to produce a curved photoresist (PR) template, where the PR acts as sacrificial layer to form wavelike arched structures. Using plasma-enhanced chemical vapor deposition (PECVD) process at low temperature, the curved PR topography can be transferred to the silicon dioxide layer. Subsequently, plasma etching can be used to fabricate the arched stripe arrays. The wavelike silicon dioxide arch microstructure exhibits Young modulus and fracture strength of 52 GPa and 300 MPa, respectively. The model of stress distribution inside the microstructure was also established, which compares well with the experimental results. This approach of fabricating a wavelike arch structure may become a promising route to produce a variety of stretchable sensors, actuators and circuits, thus providing unique opportunities for emerging classes of robust 3D integrated systems.
Efficient Generation of Corticofugal Projection Neurons from Human Embryonic Stem Cells
Authors: Zhu Xiaoqing , Ai Zongyong , Hu Xintian , Li Tianqing
Published: June 2016

Efforts to study development and function of corticofugal projection neurons (CfuPNs) in the human cerebral cortex for health and disease have been limited by the unavailability of highly enriched CfuPNs. Here, we develop a robust, two-step process for generating CfuPNs from human embryonic stem cells (hESCs): directed induction of neuroepithelial stem cells (NESCs) from hESCs and efficient differentiation of NESCs to about 80% of CfuPNs. NESCs or a NESC faithfully maintain unlimitedly self-renewal and self-organized abilities to develop into miniature neural tube-like structures. NESCs retain a stable propensity toward neuronal differentiation over culture as fate-restricted progenitors of CfuPNs and interneurons. When grafted into mouse brains, NESCs successfully integrate into the host brains, differentiate into CfuPNs and effectively reestablish specific patterns of subcortical projections and synapse structures. Efficient generation of CfuPNs in vitro and in vivo will facilitate human cortex development and offer sufficient CfuPNs for cell therapy.
Dipolar colloids in apolar media: direct microscopy of two-dimensional suspensions
Authors: Janai Erez , Cohen Avner P. , Butenko Alexander V. , Schofield Andrew B. , Schultz Moty , Sloutskin Eli
Published: June 2016

Spherical colloids, in an absence of external fields, are commonly assumed to interact solely through rotationally-invariant potentials,u(r). While the presence of permanent dipoles in aqueous suspensions has been previously suggested by some experiments, the rotational degrees of freedom of spherical colloids are typically neglected. We prove, by direct experiments, the presence of permanent dipoles in commonly used spherical poly(methyl methacrylate) (PMMA) colloids, suspended in an apolar organic medium. We study, by a combination of direct confocal microscopy, computer simulations and theory, the structure and other thermodynamical properties of organic suspensions of colloidal spheres, confined to a two-dimensional (2D) monolayer. Our studies reveal the effects of the dipolar interactions on the structure and the osmotic pressure of these fluids. These observations have far-reaching consequences for the fundamental colloidal science, opening new directions in self-assembly of complex colloidal clusters.
Gibberellin deficiency is responsible for shy-flowering nature of Epipremnum aureum
Authors: Hung Chiu-Yueh , Qiu Jie , Sun Ying-Hsuan , Chen Jianjun , Kittur Farooqahmed S. , Henny Richard J. , Jin Gulei , Fan Longjiang , Xie Jiahua
Published: June 2016

Epipremnum aureum is an extremely popular houseplant belonging to the Araceae family of angiosperms, but it does not flower either in the wild or under cultivation. We uncovered the potential causes of its shy-flowering nature by building the transcriptome using next-generation sequencing and identifying floral-related genes that are differentially expressed between vertical growth (VG, adult) and horizontal growth (HG, juvenile) plants. Transcripts of the gibberellin (GA) biosynthetic gene EaGA3ox1 and GA-responsive floral meristem identity gene EaLFY were absent in both VG and HG plants, suggesting that a deficiency of bioactive GAs may be responsible for its shy-flowering nature. This hypothesis is supported by undetectable or low levels of three bioactive GAs, and exogenous GA3 triggered flowering in both plants. Our study resolves the mystery why E. aureum fails to flower, and reveals the positive role of GAs in floral transition in perennials.
Correction: Corrigendum: Sustainable, Rapid Synthesis of Bright-Luminescent CuInS2-ZnS Alloyed Nanocrystals: Multistage Nano-xenotoxicity Assessment and Intravital Fluorescence Bioimaging in Zebrafish-Embryos
Authors: Chetty S. Shashank , Praneetha S. , Basu Sandeep , Sachidanandan Chetana , Murugan A. Vadivel
Published: June 2016

Scientific Reports 6: Article number: 26078; published online: 18 May 2016; updated: 27 June 2016. The Acknowledgements section in this Article is incomplete. “This work was financially supported by the Department of Science and Technology, Technology system development (DST-TSD) grant no. PT/2011/178-G, Government of India, New Delhi under “Development of cadmium free high-luminescence III-V and I-III-VI semiconductors based core-shell nanocrystals as nanoprobes for bioimaging applications” for providing the microwave-assisted synthesis facility in our lab.
Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics
Authors: Yoo Ji-Sun , Oh Gyeong-Seok , Ryoo Sungweon , Roe Jung-Hye
Published: June 2016

Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σR (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σR called σR′. In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σR, eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σR. The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses.
Highly efficient modulation of FRET in an orthogonally arranged BODIPY–DTE dyad
Authors: Schweighöfer Felix , Dworak Lars , Hammer Christopher A. , Gustmann Henrik , Zastrow Marc , Rück-Braun Karola , Wachtveitl Josef
Published: June 2016

The photoswitchable boron-dipyrromethene–dithienylethene molecular dyad is introduced as a prototype for the efficient fluorescence intensity modulation on the molecular level. The functionality of the system is based on the photochromism of the dithienylethene, which facilitates an efficient on- and off-switching of a Förster-type intramolecular energy transfer between the photoexcited BODIPY donor and the dithienylethene acceptor moiety. The switching behavior and dynamics of the molecular dyad are monitored by steady state and time-resolved spectroscopic methods. A quenching efficiency of up to 96% in the off-state is observed and explained by a drastically accelerated decay of the boron-dipyrromethene excited state due to the efficient energy transfer despite the orthogonal arrangement of donor and acceptor. An energy transfer time orders of magnitude shorter than the lifetime of the boron-dipyrromethene in the open state is determined.
Leptin promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-27b in human chondrosarcoma cells
Authors: Yang Wei-Hung , Chang An-Chen , Wang Shih-Wei , Wang Shoou-Jyi , Chang Yung-Sen , Chang Tzu-Ming , Hsu Shao-Keh , Fong Yi-Chin , Tang Chih-Hsin
Published: June 2016

Chondrosarcoma is the second most frequently occurring type of bone malignancy that is characterized by the distant metastasis propensity. Vascular endothelial growth factor-C (VEGF-C) is the chief lymphangiogenic mediator and makes crucial contributions to tumor lymphangiogenesis. Leptin is an adipocytokine and has been indicated to facilitate tumorigenesis, angiogenesis and metastasis. However, the effect of leptin on VEGF-C regulation and lymphangiogenesis in human chondrosarcoma has hugely remained a mystery. Our results showed a clinical correlation between leptin and VEGF-C as well as tumor stage in human chondrosarcoma tissues. We further demonstrated that leptin promoted VEGF-C production and secretion in human chondrosarcoma cells. The conditioned medium from leptin-treated chondrosarcoma cells induced lymphangiogenesis of human lymphatic endothelial cells. We also found that leptin-induced VEGF-C is mediated by the FAK, PI3K and Akt signaling pathway. Furthermore, the expression of microRNA-27b was negatively regulated by leptin via the FAK, PI3K and Akt cascade. Our study is the first to describe the mechanism of leptin-promoted lymphangiogenesis by upregulating VEGF-C expression in chondrosarcomas. Thus, leptin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.