bluuebunny/crossref_metadata_2025 huggingface dataset:
Elbasvir/grazoprevir in Asia‐Pacific/Russian participants with chronic hepatitis C virus genotype 1, 4, or 6 infection
Authors: George Jacob , Burnevich Eduard , Sheen I‐Shyan , Heo Jeong , Kinh Nguyen Van , Tanwandee Tawesak , Cheng Pin‐Nan , Kim Do Young , Tak Won Young , Kizhlo Svetlana , Zhdanov Konstantin , Isakov Vasily , Liang Liwen , Lindore Pauline , Ginanni Joy , Nguyen Bach‐Yen , Wahl Janice , Barr Eliav , Robertson Michael , Ingravallo Paul , Talwani Rohit ,   on behalf of the C‐CORAL Study Investigators
Published: April 2018

The prevalence of hepatitis C virus (HCV) infection in Asian countries is high. This study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from Asia‐Pacific countries and Russia. In this phase 3, randomized, placebo‐controlled, double‐blind study, treatment‐naive participants with HCV genotype (GT) 1, 4, or 6 infection were randomized to EBR 50 mg/GZR 100 mg (immediate‐treatment group [ITG]) or placebo (deferred‐treatment group [DTG]) once daily for 12 weeks (Protocol PN‐5172‐067, NCT02251990). The primary efficacy variable was a nonrandomized comparison of sustained virologic response at 12 weeks after the end of therapy (SVR12) for the ITG with a historical control. The primary safety outcome was a randomized comparison between the ITG and DTG. Three hundred thirty‐seven participants were randomized to the ITG (n = 251) or DTG (n = 86); 199 (59.2%) participants were Asian, and 250 (74.4%) had HCV GT1b infection. Overall, 232/250 (92.8%) participants in the ITG achieved SVR12 (97.5% confidence interval, 89.1, 96.5). Of the 18 participants who failed to attain SVR12, 1 was lost to follow‐up and 17 had virologic failure, 13 of whom had HCV GT6 infection. The incidence of adverse events was similar between participants receiving EBR/GZR and placebo (50.8% versus 51.2%; difference, −0.3%; 95% confidence interval, −12.3, 11.9). Conclusion: EBR/GZR for 12 weeks provides an effective and well‐tolerated regimen for chronic HCV GT1 infection in treatment‐naive people from Asia‐Pacific countries and Russia, particularly for the large population with GT1b infection. EBR/GZR is not recommended for the treatment of individuals with HCV GT6 infection. (Hepatology Communications 2018;2:595‐606)
Precision of Four Otolith Techniques for Estimating Age of White Perch from a Thermally Altered Reservoir
Authors: Snow Richard A. , Porta Michael J. , Long James M.
Published: April 2018

The White Perch Morone americana is an invasive species in many Midwestern states and is widely distributed in reservoir systems, yet little is known about the species' age structure and population dynamics. White Perch were first observed in Sooner Reservoir, a thermally altered cooling reservoir in Oklahoma, by the Oklahoma Department of Wildlife Conservation in 2006. It is unknown how thermally altered systems like Sooner Reservoir may affect the precision of White Perch age estimates. Previous studies have found that age structures from Largemouth Bass Micropterus salmoides and Bluegills Lepomis macrochirus from thermally altered reservoirs had false annuli, which increased error when estimating ages. Our objective was to quantify the precision of White Perch age estimates using four sagittal otolith preparation techniques (whole, broken, browned, and stained). Because Sooner Reservoir is thermally altered, we also wanted to identify the best month to collect a White Perch age sample based on aging precision. Ages of 569 White Perch (20–308 mm TL) were estimated using the four techniques. Age estimates from broken, stained, and browned otoliths ranged from 0 to 8 years; whole-view otolith age estimates ranged from 0 to 7 years. The lowest mean coefficient of variation (CV) was obtained using broken otoliths, whereas the highest CV was observed using browned otoliths. July was the most precise month (lowest mean CV) for estimating age of White Perch, whereas April was the least precise month (highest mean CV). These results underscore the importance of knowing the best method to prepare otoliths for achieving the most precise age estimates and the best time of year to obtain those samples, as these factors may affect other estimates of population dynamics.
Giant Negative and Positive Electrocaloric Effects Coexisting in Lead‐Free Na0.5Bi4.5Ti4O15 Films Over a Broad Temperature Range
Authors: Chen Jieyu , Tang Zhehong , Zhao Shifeng
Published: April 2018

Giant negative and positive electrocaloric effects (ECEs) coexist in lead‐free Na0.5Bi4.5Ti4O15 (NBTO) ferroelectric films with layered perovskite structure over a broad temperature range, with ΔT peaks of −14.8 °C (at 273 K) in the negative electrocaloric (EC) region (273–328 K), of 3.45 °C (at 373 K) in the positive EC region (328–418 K) and of −6.76 °C (at 483 K) in another negative EC region (418–513 K), respectively, under the electric field of 900 kV cm−1. Such giant ECEs are attributed to both the high break‐down electric field and prominent ferroelectricity. And the coexistence originates in the competition of the dipole polarization between both Na0.5Bi0.5TiO3 (NBT) and Bi4Ti3O12 (BTO) cells of NBTO films over the whole temperature region. Furthermore, the outstanding anti‐fatigue features with temperature stability for NBTO films ensure the durability of EC refrigeration. This work will prompt a novel technology for next generation of environmental‐friendly solid‐state cooling devices.
Higher spin algebras and large $$ \mathcal{N} $$ = 4 holography
Authors: Eberhardt Lorenz , Gaberdiel Matthias R. , Rienäcker Ingo
Published: April 2018

Abstract

A new family of higher spin algebras that arises upon restricting matrix extensions of

$$ \mathfrak{s}\mathfrak{h}\mathfrak{s}\left[\lambda \right] $$

s
h
s

λ

is found. We identify coset CFTs realising these symmetry algebras, and thus propose new higher spin-CFT dual pairs. These higher spin theories arise naturally as a subsector of string theory on AdS3 × S3 × S3 × S1 for specific ratios of the radii of the two spheres.
Collider constraints on light pseudoscalars
Authors: Haisch Ulrich , Kamenik Jernej F. , Malinauskas Augustinas , Spira Michael
Published: April 2018

Abstract

We investigate the bounds on light pseudoscalars that arise from a variety of collider searches. Special attention is thereby devoted to the mass regions [3, 5] GeV and [9, 11] GeV, in which a meaningful theoretical description has to include estimates of non-perturbative effects such as the mixing of the pseudoscalar with QCD bound states. A compendium of formulas that allows to deal with the relevant corrections is provided. It should prove useful for the interpretation of future LHC searches for light CP-odd spin-0 states.
Neutrino mass generation at TeV scale and new physics signatures from charged Higgs at the LHC for photon initiated processes
Authors: Ghosh Kirtiman , Jana Sudip , Nandi S.
Published: April 2018

Abstract

We consider the collider phenomenology of a simple extension of the Standard Model (SM), which consists of an EW isospin 3/2 scalar, Δ and a pair of EW isospin 1 vector like fermions, Σ and

$$ \overline{\varSigma} $$

Σ
¯

, responsible for generating tiny neutrino mass via the effective dimension seven operator. This scalar quadruplet with hypercharge Y = 3 has a plethora of implications at the collider experiments. Its signatures at TeV scale colliders are expected to be seen, if the quadruplet masses are not too far above the electroweak symmetry breaking scale. In this article, we study the phenomenology of multi-charged quadruplet scalars. In particular, we study the multi-lepton signatures at the Large Hadron Collider (LHC) experiment, arising from the production and decays of triply and doubly charged scalars. We studied Drell-Yan (DY) pair production as well as pair production of the charged scalars via photon-photon fusion. For doubly and triply charged scalars, photon fusion contributes significantly for large scalar masses. We also studied LHC constraints on the masses of doubly charged scalars in this model. We derive a lower mass limit of 725 GeV on doubly charged quadruplet scalar.
Involvement and Influence of Healthcare Providers, Family Members, and Other Mutation Carriers in the Cancer Risk Management Decision‐Making Process of BRCA1 and BRCA2 Mutation Carriers
Authors: Puski Athena , Hovick Shelly , Senter Leigha , Toland Amanda Ewart
Published: April 2018

Deciding between increased cancer screening or prophylactic surgery and the timing of such procedures can be a difficult and complex process for women with BRCA mutations. There are gaps in our understanding of involvement of others in the decision‐making process for women with BRCA mutations. This study evaluated the management decision‐making process of women with BRCA mutations, focusing on the involvement of others. Grounded theory was used to analyze and code risk management decision‐making information from interviews with 20 BRCA mutation carriers. Unaffected at‐risk participants with a BRCA mutation, those under age 40, and those with no children described having a difficult time making risk management decisions. Physicians were an integral part of the decision‐making process by providing decisional support and management recommendations. Family members and other mutation carriers filled similar yet distinct roles by providing experiential information as well as decisional and emotional support for carriers. Participants described genetic counselors as short‐term providers of risk information and management recommendations. The study findings suggest that unaffected at‐risk women, women under 40, and those who do not have children may benefit from additional support and information during the decision‐making process. Genetic counselors are well trained to help women through this process and connect them with resources, and may be under‐utilized in long‐term follow‐up for women with a BRCA mutation.
Less Midterm Damage and Oxidation Are Seen in Retrieved Highly Crosslinked Ultrahigh-Molecular-Weight Polyethylene Tibial Inserts than in Direct Compression Molded Polyethylene Inserts
Authors: Stavrakis Alexandra , Weitzler Lydia , Wright Timothy , Padgett Douglas E.
Published: April 2018

Background

Highly crosslinked ultrahigh-molecular-weight polyethylene (XLPE) shows reduced wear in total hip arthroplasty compared to direct compression-molded polyethylene (compPE); however, minimal research evaluating polyethylene damage in XLPE tibial inserts in total knee arthroplasty exists.

Questions/Purposes

We evaluated damage and material properties in retrieved XLPE components at midterm (≥ 2.5 years) follow-up.

Methods

We identified 19 XLPE tibial inserts with ≥ 30 months in vivo using our institutional review board–approved implant retrieval system; 19 compPE retrieved inserts were matched based on age at index surgery, body mass index, sex, and length of implantation. Articular surface damage was assessed using a subjective grading system. Swell ratio testing and Fourier-transform infrared spectroscopy were used to measure crosslink density (XLPE) and oxidation (XLPE, compPE), respectively, at loaded and unloaded surface and subsurface regions.

Results

CompPE inserts had higher overall damage than XLPE inserts, specifically at the post of posterior-stabilized inserts. The XLPE inserts had lower crosslink density at the loaded surface (0.159 mol/dm3) than either unloaded region (0.183 mol/dm3). CompPE peak oxidation index (OI) was greater than XLPE peak OI in the loaded and unloaded surface regions (1.67 vs. 0.61 and 1.38 vs. 0.46, respectively).

Conclusions

Surface damage and oxidation are reduced in XLPE inserts compared to compPE at midterm follow-up. Peak OI greater than 1.0 in the compPE group suggests that mechanical-property degradation had occurred, a likely cause for increased damage. Longer-term retrievals will determine whether these trends continue. Based on midterm results, XLPE shows an advantage over compression molded PE in total knee arthroplasty.
Use of risk assessment instruments to predict violence in forensic psychiatric hospitals: a systematic review and meta-analysis
Authors: Ramesh Taanvi , Igoumenou Artemis , Vazquez Montes Maria , Fazel Seena
Published: April 2018

Background and Aims:

Violent behaviour by forensic psychiatric inpatients is common. We aimed to systematically review the performance of structured risk assessment tools for violence in these settings.

Methods:

The nine most commonly used violence risk assessment instruments used in psychiatric hospitals were examined. A systematic search of five databases (CINAHL, Embase, Global Health, PsycINFO and PubMed) was conducted to identify studies examining the predictive accuracy of these tools in forensic psychiatric inpatient settings. Risk assessment instruments were separated into those designed for imminent (within 24 hours) violence prediction and those designed for longer-term prediction. A range of accuracy measures and descriptive variables were extracted. A quality assessment was performed for each eligible study using the QUADAS-2. Summary performance measures (sensitivity, specificity, positive and negative predictive values, diagnostic odds ratio, and area under the curve value) and HSROC curves were produced. In addition, meta-regression analyses investigated study and sample effects on tool performance.

Results:

Fifty-two eligible publications were identified, of which 43 provided information on tool accuracy in the form of AUC statistics. These provided data on 78 individual samples, with information on 6,840 patients. Of these, 35 samples (3,306 patients from 19 publications) provided data on all performance measures. The median AUC value for the wider group of 78 samples was higher for imminent tools (AUC 0.83; IQR: 0.71–0.85) compared with longer-term tools (AUC 0.68; IQR: 0.62-0.75). Other performance measures indicated variable accuracy for imminent and longer-term tools. Meta-regression indicated that no study or sample-related characteristics were associated with between-study differences in AUCs.

Interpretation:

The performance of current tools in predicting risk of violence beyond the first few days is variable, and the selection of which tool to use in clinical practice should consider accuracy estimates. For more imminent violence, however, there is evidence in support of brief scalable assessment tools.
Why do the dark and light ogives of Forbes bands have similar surface mass balances?
Authors: VINCENT C. , DUMONT M. , SIX D. , BRUN F. , PICARD G. , ARNAUD L.
Published: April 2018

Band ogives are a striking and enigmatic feature of Mer de Glace glacier flow. The surface mass balances (SMBs) of these ogives have been thoroughly investigated over a period of 12 years. We find similar cumulative SMBs over this period, ranging between −64.1 and −66.2 m w.e., on the dark and light ogives even though the dark ogive albedo is ~40% lower than that of the light ogives. We, therefore, looked for another process that could compensate for the large difference of absorbed short-wave radiation between dark and light ogives. Based on in situ roughness measurements, our numerical modeling experiments demonstrate that a significant difference in turbulent flux over the dark and light ogives due to different surface roughnesses could compensate for the difference in radiative forcing. Our results discard theories for the genesis of band ogives that are based on the assumption of a strong ice ablation contrast between dark and light ogives. More generally, our study demonstrates that future roughness changes are as important to analyze as the radiative impacts of a potential increase of aerosols or debris at the surface of glaciers.
Four new species of the Jurassic to Cretaceous seep-restricted bivalveCaspiconchaand implications for the history of chemosynthetic communities
Authors: Jenkins Robert G. , Kaim Andrzej , Hikida Yoshinori , Kiel Steffen
Published: April 2018

Four new species of the methane seep-inhabiting kalenterid bivalve genusCaspiconchaKelly in Kelly et al., 2000 are described:Caspiconcha basquensisfrom the late Albian of northern Spain,C. yubariensisfrom the late Albian of northern Japan,C. raukumaraensisfrom the late Albian to mid-Cenomanian of New Zealand, andC. lastsamuraifrom the Campanian of northern Japan. The earliest confirmed record of the genus is known from the latest Jurassic. It reached its maximum diversity in the Albian and declined in diversity and abundance through the Late Cretaceous. The youngest species,C. lastsamurai, is currently known from a single specimen only.

UUID:http://zoobank.org/2f84cfd3-216c-4f1b-8c9f-c808a47f7aaa
Streptococcal group A, C and G pharyngitis in school children: a prospective cohort study in Southern India
Authors: Jose J. John Melbin , Brahmadathan Kootallur N. , Abraham Vinod J. , Huang Chiung-Yu , Morens David , Hoe Nancy P. , Follmann Dean A. , Krause Richard M.
Published: April 2018

Diagnosing streptococcal pharyngitis in children on the basis of clinical appearance and throat culture is complicated by high colonisation rates and by the ability of other pathogens to cause clinically similar disease. To characterise the epidemiology of Lancefield Group A, C and G β-haemolytic streptococcus (GAS, GCS and GGS, respectively) in children, we conducted a 2-year prospective study of 307 school children between 7 and 11 years old. GGS and GAS were commonly identified organisms both for silent streptococcal colonisation and symptomatic sore throat, while GCS was uncommonly found. Streptococcal culture positivity at the time of clinical pharyngitis was estimated to reflect true streptococcal pharyngitis in only 26% of instances, with the frequency varying from 54% for children rarely colonised to 1% for children frequently colonised. Numerous GAS emm types were identified, including several types previously associated with severe pharyngitis (e.g. emm types 1, 3 and 28). No severe complications were seen in any child. These data suggest that the clinical diagnosis of streptococcal pharyngitis is likely to remain difficult and that treatment decisions will remain clouded by uncertainty. There remains a need for organism-specific rapid point-of-care streptococcal diagnostic tests and tests that can distinguish between streptococcal colonisation and disease.
A minor majority
Authors: Lokko Lesley
Published: April 2018

The terms ‘age of consent’, ‘age of licence’ and ‘age of majority’ – often used interchangeably – give young adults legal and moral permission to drink, drive, vote, smoke, have sex and marry (among other rights). Depending on context, the threshold from being a minor to attaining majority – adulthood – is marked by a ritual or a ceremony, giving the threshold cul-tural as well as legal significance. But thresholds, as we already know, are places of action, movement, change … rarely comfortable or easy, and seldom precise. Drawing on the three years since the Graduate School of Architecture at the University of Johannesburg (GSA) was established in 2016, this essay traces the school's own ‘coming-of-age’ in a time of violent protest and popular uprising against an out-of-date and stubbornly Eurocentric curriculum. Whilst the issues facing young South African students – both black and white – have particular resonance inside South Africa, many of the initiatives that the school has pioneered under the banner of ‘Transformative Pedagogies’ hold meaning for the rest of the African continent. Using a mixture of conventional texts, videos, projects and transcripts, A Minor Majority details the GSA's attempts to seize both the site-specific ‘winds of change’ in South Africa and take advantage of global shifts in research culture and methodology to arrive at new insights and possibilities.
Is architectural history getting any bigger?
Authors: Hyde Timothy
Published: April 2018

Vincent Scully's recent death serves as reminder that the discipline of architectural history is not so old, with only a few intellectual generations needed to skip back to the turn of the twentieth century. Heinrich Wölfflin died in 1945 and Scully started writing his dissertation the following year, under the supervision of Henry-Russell Hitchcock. James Ackerman, whose death was also recent, co-taught with Scully in those years while being advised by Richard Krautheimer, who had completed his own dissertation under Paul Frankl. Students of both Scully and Ackerman are today adjusting the contours of the field with their books, articles, and lectures.

The scope of the development of architectural history is perhaps more limited than chronological age might suggest, and certainly that in comparison to the existence of its presumed subject matter – architecture – has barely made it to infancy. Without diminishing the hours of archival labour, field work, and writing that have been undertaken over the past century and a half, and without understating the contributions to knowledge and understanding those efforts have produced, the implication should be admitted: there really isn't very much architectural history. Not that many architectural historians, not that many books, not that much history, relatively speaking. This is not necessarily to say that architectural history is marginal, for it has attained points of instrumentality and effect along the way, but the admission is the necessary starting point for reflection on the future of the discipline, because architectural history needs to think about how to get bigger.
Assessment of Management Options onStrigaInfestation and Maize Grain Yield in Kenya
Authors: Kanampiu Fred , Makumbi Dan , Mageto Edna , Omanya Gospel , Waruingi Sammy , Musyoka Peter , Ransom Joel
Published: April 2018

The parasitic purple witchweed [Striga hermonthica(Del.) Benth.] is a serious constraint to maize production in sub-Saharan Africa, especially in poor soils. VariousStrigaspp. control measures have been developed, but these have not been assessed in an integrated system. This study was conducted to evaluate a set of promising technologies forS. hermonthicamanagement in western Kenya. We evaluated three maize genotypes either intercropped with peanut (Arachis hypogaeaL.), soybean [Glycine max(L.) Merr.], or silverleaf desmodium [Desmodium uncinatum(Jacq.) DC] or as a sole crop at two locations under artificialS. hermonthicainfestation and at three locations under naturalS. hermonthicainfestation between 2011 and 2013. Combined ANOVA showed significant (P<0.05) cropping system and cropping system by environment interactions for most traits measured. Grain yield was highest for maize grown in soybean rotation (3,672 kg ha−1) under artificial infestation and inD. uncinatumand peanut cropping systems (3,203 kg ha−1and 3,193 kg ha−1) under natural infestation. Grain yield was highest for theStrigaspp.-resistant hybrid under both methods of infestation. A lower number of emergedS. hermonthicaplants per square meter were recorded at 10 and 12 wk after planting on maize grown underD. uncinatumin the artificialS. hermonthicainfestation. A combination of herbicide-resistant maize varieties intercropped with legumes was a more effective method forS. hermonthicacontrol than individual-component technologies. Herbicide-resistant andStrigaspp.-resistant maize integrated with legumes would help reduce theStrigaspp. seedbank in the soil. Farmers should be encouraged to adopt an integrated approach to controlStrigaspp. for better maize yields.
Kognitive Verzerrungen und Metakognition bei Multipler Sklerose (MS)
Authors: Pöttgen Jana
Published: April 2018

Zusammenfassung. Neben einer Reihe physischer Beeinträchtigungen sind die psychischen und kognitiven Störungen bei Multipler Sklerose (MS) seit einigen Jahren im Fokus von Patienten und Behandlern. Funktionale und kompensatorische Therapieansätze konnten bisher jedoch nur bescheidene rehabilitative Erfolge vorweisen. Der Umgang mit diesen Beeinträchtigungen und die Bewältigung der damit einhergehenden Herausforderungen erscheinen gut für kognitiv-behaviorale Therapieansätze geeignet. Vor diesem Hintergrund wurde das Metakognitive und alltagsrelevante Training für Patienten mit Multipler Sklerose (MaTiMS) mit einem Fokus auf spezifische kognitive und psychische Beeinträchtigungen bei MS entwickelt und adressiert mithilfe eines metakognitiven Ansatzes zugrunde liegende kognitive Verzerrungen. Weitere vergleichbare therapeutische Entwicklungen für MS-Patienten gibt es bisher keine. Diese Übersichtsarbeit soll einen Überblick über typische kognitive Verzerrungen bei MS und deren Behandlung geben.
Relations Between the Behavioral Approach System (BAS) and Self-Reported Life History Traits
Authors: Krupić Dino , Banai Benjamin , Corr Philip J.
Published: April 2018

Abstract. The behavioral approach system (BAS) has been shown to be important in everyday life. However, its putative evolutionary origins have not been extensively studied. The purpose of this study was to explore relationships between BAS processes and life history strategies, or lifestyles, within life history theory. The BAS scales were assessed by the Reinforcement Sensitivity Theory of Personality Questionnaire (RST-PQ) and Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ-20), while lifestyles were measured by the Mini-K. Data from 457 participants (173 males) were analyzed by structural equation modelling, followed by set correlation to examine personality and Mini-K relationships. The structural model showed that RST-PQ Reward Interest, Goal-Drive Persistence and Reward Reactivity correlated with a slow lifestyle, while RST-PQ Impulsivity and (SPSRQ) Sensitivity to Reward (SR) did not correlate with the Mini-K. However, set correlation analysis revealed that SR correlated negatively with the Mini-K subscale Experience in romantic relationship and highlighted the importance of Insight, planning, and control in explaining the role of the BAS within slow lifestyle strategy. The findings are discussed in terms of possible evolutionary origins of the BAS.
Oil Spill Response Knowledge Grows, but New Risks Emerge
Authors: Shields Laura
Published: April 2018

Oil spill expert Nancy Kinner discusses lessons learned from Deepwater Horizon, dangers of aging infrastructure and atomized dispersants, and a Russian plan that imperils Arctic waters.
Capillary pumping independent of the liquid surface energy and viscosity
Authors: Guo Weijin , Hansson Jonas , van der Wijngaart Wouter
Published: April 2018

Capillary pumping is an attractive means of liquid actuation because it is a passive mechanism, i.e., it does not rely on an external energy supply during operation. The capillary flow rate generally depends on the liquid sample viscosity and surface energy. This poses a problem for capillary-driven systems that rely on a predictable flow rate and for which the sample viscosity or surface energy are not precisely known. Here, we introduce the capillary pumping of sample liquids with a flow rate that is constant in time and independent of the sample viscosity and sample surface energy. These features are enabled by a design in which a well-characterized pump liquid is capillarily imbibed into the downstream section of the pump and thereby pulls the unknown sample liquid into the upstream pump section. The downstream pump geometry is designed to exert a Laplace pressure and fluidic resistance that are substantially larger than those exerted by the upstream pump geometry on the sample liquid. Hence, the influence of the unknown sample liquid on the flow rate is negligible. We experimentally tested pumps of the new design with a variety of sample liquids, including water, different samples of whole blood, different samples of urine, isopropanol, mineral oil, and glycerol. The capillary filling speeds of these liquids vary by more than a factor 1000 when imbibed to a standard constant cross-section glass capillary. In our new pump design, 20 filling tests involving these liquid samples with vastly different properties resulted in a constant volumetric flow rate in the range of 20.96–24.76 μL/min. We expect this novel capillary design to have immediate applications in lab-on-a-chip systems and diagnostic devices.
Role of carnitine and its derivatives in the development and management of type 2 diabetes
Authors: Bene Judit , Hadzsiev Kinga , Melegh Bela
Published: April 2018

Type 2 diabetes is a highly prevalent chronic metabolic disorder characterized by hyperglycemia and associated with several complications such as retinopathy, hyperlipidemia and polyneuropathy. The dysregulated fatty acid metabolism along with tissue lipid accumulation is generally assumed to be associated in the development of insulin resistance and T2D. Moreover, several studies suggest a central role for oxidative stress in the pathogenesis of the disease. Since L-carnitine (LC) has an indispensable role in lipid metabolism via its involvement in the β-oxidation of long-chain fatty acids and it has antioxidant properties as well, carnitine supplementation may prove to be an effective tool in the management of the clinical course of T2D. In this review we summarize the results from animal and clinical studies demonstrating the effects of supplementation with LC or LC derivatives (acetyl-LC, propionyl-LC) on various metabolic and clinical parameters associated with T2D.
Vegetarian diet, change in dietary patterns, and diabetes risk: a prospective study
Authors: Chiu Tina H. T. , Pan Wen-Harn , Lin Ming-Nan , Lin Chin-Lon
Published: April 2018

Background/objectives

Vegetarian diets are inversely associated with diabetes in Westerners but their impact on Asians—whose pathophysiology differ from Westerners—is unknown. We aim to investigate the association between a vegetarian diet, change in dietary patterns and diabetes risk in a Taiwanese Buddhist population.

Methods

We prospectively followed 2918 non-smoking, non-alcohol drinking Buddhists free of diabetes, cancer, and cardiovascular diseases at baseline, for a median of 5 years, with 183 incident diabetes cases confirmed. Diet was assessed through a validated food frequency questionnaire at baseline and a simple questionnaire during follow-ups. Incident cases of diabetes were ascertained through follow-up questionnaires, fasting glucose and HbA1C. Stratified Cox Proportional Hazards Regression was used to assess the effect of diets on risk of diabetes.

Results

Consistent vegetarian diet was associated with 35% lower hazards (HR: 0.65, 95% CI: 0.46, 0.92), while converting from a nonvegetarian to a vegetarian pattern was associated with 53% lower hazards (HR: 0.47, 95% CI: 0.30, 0.71) for diabetes, comparing with nonvegetarians while adjusting for age, gender, education, physical activity, family history of diabetes, follow-up methods, use of lipid-lowering medications, and baseline BMI.

Conclusion

Vegetarian diet and converting to vegetarian diet may protect against diabetes independent of BMI among Taiwanese.
Geographical variation in the prevalence of obesity, metabolic syndrome, and diabetes among US adults
Authors: Gurka Matthew J. , Filipp Stephanie L. , DeBoer Mark D.
Published: April 2018

Cardiovascular disease (CVD) and type 2 diabetes remain significant public health concerns. Targeting of prevention efforts by geographical location has been suggested by the Institute of Medicine to coincide with the presence of area-based risk. The metabolic syndrome (MetS) is a stronger risk factor than is obesity for the prediction of future CVD and diabetes, yet its prevalence has not previously been described geographically. Our objective is to determine geographical variation in the prevalence of obesity, MetS, and diabetes among US adults. We assessed the prevalence of obesity, MetS, and diabetes by US census division, and the prevalence of obesity, MetS, and diabetes for each sex and racial/ethnic group by US region among 9826 US non-Hispanic white, non-Hispanic black, and Hispanic adults aged 20–65 years participating in the National Health and Nutrition Examination Survey 1999–2014. We also compared a sex- and race/ethnicity-specific MetS severity score by geographical area. The prevalence of obesity, MetS, and diabetes varied by US census division and region, with overall similarity by geographical area in the prevalence of each of these conditions. The prevalence of MetS was particularly high (≥35%) in the West North Central, West South Central, and East South Central and low (30%) in the Pacific, New England, and Mid-Atlantic divisions. Some of the geographical variation appeared due to differences among non-Hispanic white females, who had a high prevalence of MetS (>32%) in the Midwest and South and a low prevalence of MetS (24%) in the West and Northeast. Geographical differences in MetS imply variation in the risk for future CVD and diabetes, with more elevated risk in the center of the United States. As MetS is a stronger risk factor for prediction of CVD and T2DM than is obesity, these differences are potentially important for prompting public health efforts toward surveillance and prevention in high-risk areas.
Stress-induced phosphoprotein 1 acts as a scaffold protein for glycogen synthase kinase-3 beta-mediated phosphorylation of lysine-specific demethylase 1
Authors: Tsai Chia-Lung , Chao An-Shine , Jung Shih-Ming , Lin Chiao-Yun , Chao Angel , Wang Tzu-Hao
Published: April 2018

Stress-induced phosphoprotein 1 (STIP1)—a co-chaperone of heat shock proteins—promotes cell proliferation and may act as an oncogenic factor. Similarly, glycogen synthase kinase-3 beta (GSK3β)-mediated phosphorylation of lysine-specific demethylase 1 (LSD1)—an epigenetic regulator—can contribute to the development of an aggressive cell phenotype. Owing to their ability to tether different molecules into functional complexes, scaffold proteins have a key role in the regulation of different signaling pathways in tumorigenesis. Here, we show that STIP1 acts as a scaffold promoting the interaction between LSD1 and GSK3β. Specifically, the TPR1 and TPR2B domains of STIP1 are capable of binding with the AOL domain of LSD1, whereas the TPR2A and TPR2B domains of STIP1 interact with the kinase domain of GSK3β. We also demonstrate that STIP1 is required for GSK3β-mediated LSD1 phosphorylation, which promoted LSD1 stability and enhanced cell proliferation. After transfection of cancer cells with double-mutant (S707A/S711A) LSD1, subcellular localization analysis revealed that LSD1 was translocated from the nucleus to the cytoplasm. In vitro experiments also showed that the LSD1 inhibitor SP2509 and the GSK3β inhibitor LY2090314 acted synergistically to induce cancer cell death. Finally, the immunohistochemical expression of STIP1 and LSD1 showed a positively correlation in human cancer specimens. In summary, our data provide mechanistic insights into the role of STIP1 in human tumorigenesis by showing that it serves as a scaffold for GSK3β-mediated LSD1 phosphorylation. The combination of LSD1 and GSK3β inhibitors may exert synergistic antitumor effects and deserves further scrutiny in preclinical studies.
Targeting MDMX and PKCδ to improve current uveal melanoma therapeutic strategies
Authors: Heijkants R. C. , Nieveen M. , Hart K. C.’t , Teunisse A. F. A. S. , Jochemsen A. G.
Published: April 2018

Uveal melanoma (UM) is the most frequent ocular cancer in adults, accounting for ~5% of the total melanoma incidence. Although the primary tumor is well treatable, patients frequently develop metastases for which no curative therapy exists. Highly activated protein kinase C (PKC) is a common feature of UM and has shown potential as therapeutic intervention for UM patients. Unfortunately, PKC inhibition as single treatment appears to have only limited clinical benefit. Combining PKC inhibition with activation of p53, which is rarely mutated in UM, by MDM2 inhibitors has shown promising results in vitro and in vivo. However, clinical studies have shown strong adverse effects of MDM2 inhibition. Therefore, we investigated alternative approaches to achieve similar anticancer effects, but with potentially less adverse effects. We studied the potential of targeting MDMX, an essential p53 inhibitor during embryonal development but less universally expressed in adult tissues compared with MDM2. Therefore, targeting MDMX is predicted to have less adverse effects in patients. Depletion of MDMX, like the pharmacological activation of p53, inhibits the survival of UM cells, which is enhanced in combination with PKC inhibition. Also pan-PKC inhibitors elicit adverse effects in patients. As the PKC family consists of 10 different isoforms, it could be hypothesized that targeting a single PKC isoform would have less adverse effects compared with a pan-PKC inhibitor. Here we show that specifically depleting PKCδ inhibits UM cell growth, which can be further enhanced by p53 reactivation. In conclusion, our data show that the synergistic effects of p53 activation by MDM2 inhibition and broad spectrum PKC inhibition on survival of UM cells can also largely be achieved by the presumably less toxic combination of depletion of MDMX and targeting a specific PKC isoform, PKCδ.
Cultivation and genomics of the first freshwater SAR11 (LD12) isolate
Authors: Henson Michael W , Lanclos V Celeste , Faircloth Brant C , Thrash J Cameron
Published: April 2018

Evolutionary transitions between fresh and salt water happen infrequently among bacterioplankton. Within the ubiquitous and highly abundant heterotrophic Alphaproteobacteria order Pelagibacterales (SAR11), most members live in marine habitats, but the LD12 subclade has evolved as a unique freshwater lineage. LD12 cells occur as some of the most dominant freshwater bacterioplankton, yet this group has remained elusive to cultivation, hampering a more thorough understanding of its biology. Here, we report the first successful isolation of an LD12 representative, strain LSUCC0530, using high-throughput dilution-to-extinction cultivation methods, and its complete genome sequence. Growth experiments corroborate ecological data suggesting active populations of LD12 in brackish water up to salinities of ~5. LSUCC0530 has the smallest closed genome thus far reported for a SAR11 strain (1.16 Mbp). The genome affirms many previous metabolic predictions from cultivation-independent analyses, like a complete Embden–Meyerhof–Parnas glycolysis pathway, but also provides novel insights, such as the first isocitrate dehydrogenase in LD12, a likely homologous recombination of malate synthase from outside of the SAR11 clade, and analogous substitutions of ion transporters with others that occur throughout the rest of the SAR11 clade. Growth data support metagenomic recruitment results suggesting temperature-based ecotype diversification within LD12. Key gene losses for osmolyte uptake provide a succinct hypothesis for the evolutionary transition of LD12 from salt to freshwater. For strain LSUCC0530, we propose the provisional nomenclature Candidatus fonsibacter ubiquis.
Grazer-induced transcriptomic and metabolomic response of the chain-forming diatom Skeletonema marinoi
Authors: Amato Alberto , Sabatino Valeria , Nylund Göran M , Bergkvist Johanna , Basu Swaraj , Andersson Mats X , Sanges Remo , Godhe Anna , Kiørboe Thomas , Selander Erik , Ferrante Maria I
Published: April 2018

Diatoms and copepods are main actors in marine food webs. The prey–predator interactions between them affect bloom dynamics, shape marine ecosystems and impact the energy transfer to higher trophic levels. Recently it has been demonstrated that the presence of grazers may affect the diatom prey beyond the direct effect of grazing. Here, we investigated the response of the chain-forming centric diatom Skeletonema marinoi to grazer cues, including changes in morphology, gene expression and metabolic profile. S. marinoi cells were incubated with Calanus finmarchicus or with Centropages typicus and in both cases responded by reducing the chain length, whereas changes in gene expression indicated an activation of stress response, changes in the lipid and nitrogen metabolism, in cell cycle regulation and in frustule formation. Transcripts linked to G protein-coupled receptors and to nitric oxide synthesis were differentially expressed suggesting involvement of these signalling transduction pathways in the response. Downregulation of a lipoxygenase in the transcriptomic data and of its products in the metabolomic data also indicate an involvement of oxylipins. Our data contribute to a better understanding of the gene function in diatoms, providing information on the nature of genes implicated in the interaction with grazers, a crucial process in marine ecosystems.
Population genomic analysis of the rice blast fungus reveals specific events associated with expansion of three main clades
Authors: Zhong Zhenhui , Chen Meilian , Lin Lianyu , Han Yijuan , Bao Jiandong , Tang Wei , Lin Lili , Lin Yahong , Somai Rewish , Lu Lin , Zhang Wenjing , Chen Jian , Hong Yonghe , Chen Xiaofeng , Wang Baohua , Shen Wei-Chiang , Lu Guodong , Norvienyeku Justice , Ebbole Daniel J , Wang Zonghua
Published: April 2018

We examined the genomes of 100 isolates of Magnaporthe oryzae (Pyricularia oryzae), the causal agent of rice blast disease. We grouped current field populations of M. oryzae into three major globally distributed groups. A genetically diverse group, clade 1, which may represent a group of closely related lineages, contains isolates of both mating types. Two well-separated clades, clades 2 and 3, appear to have arisen as clonal lineages distinct from the genetically diverse clade. Examination of genes involved in mating pathways identified clade-specific diversification of several genes with orthologs involved in mating behavior in other fungi. All isolates within each clonal lineage are of the same mating type. Clade 2 is distinguished by a unique deletion allele of a gene encoding a small cysteine-rich protein that we determined to be a virulence factor. Clade 3 isolates have a small deletion within the MFA2 pheromone precursor gene, and this allele is shared with an unusual group of isolates we placed within clade 1 that contain AVR1-CO39 alleles. These markers could be used for rapid screening of isolates and suggest specific events in evolution that shaped these populations. Our findings are consistent with the view that M. oryzae populations in Asia generate diversity through recombination and may have served as the source of the clades 2 and 3 isolates that comprise a large fraction of the global population.
Demographic fluctuation of community-acquired antibiotic-resistant Staphylococcus aureus lineages: potential role of flimsy antibiotic exposure
Authors: Gustave Claude-Alexandre , Tristan Anne , Martins-Simões Patricia , Stegger Marc , Benito Yvonne , Andersen Paal Skytt , Bes Michèle , Le Hir Typhanie , Diep Binh An , Uhlemann Anne-Catrin , Glaser Philippe , Laurent Frédéric , Wirth Thierry , Vandenesch François
Published: April 2018

Community-acquired (CA)- as opposed to hospital acquired- methicillin-resistant Staphylococcus aureus (MRSA) lineages arose worldwide during the 1990s. To determine which factors, including selective antibiotic pressure, govern the expansion of two major lineages of CA-MRSA, namely “USA300” in Northern America and “European ST80” in North Africa, Europe and Middle-East, we explored virulence factor expression, and fitness levels with or without antibiotics. The sampled strains were collected in a temporal window representing various steps of the epidemics, reflecting predicted changes in effective population size as inferred from whole-genome analysis. In addition to slight variations in virulence factor expression and biofilm production that might influence the ecological niches of theses lineages, competitive fitness experiments revealed that the biological cost of resistance to methicillin, fusidic acid and fluoroquinolones is totally reversed in the presence of trace amount of antibiotics. Our results suggest that low-level antibiotics exposure in human and animal environments contributed to the expansion of both European ST80 and USA300 lineages in community settings. This surge was likely driven by antibiotic (ab)use promoting the accumulation of antibiotics as environmental pollutants. The current results provide a novel link between effective population size increase of a pathogen and a selective advantage conferred by antibiotic resistance.
Lateral habenula perturbation reduces default-mode network connectivity in a rat model of depression
Authors: Clemm von Hohenberg Christian , Weber-Fahr Wolfgang , Lebhardt Philipp , Ravi Namasivayam , Braun Urs , Gass Natalia , Becker Robert , Sack Markus , Cosa Linan Alejandro , Gerchen Martin Fungisai , Reinwald Jonathan Rochus , Oettl Lars-Lennart , Meyer-Lindenberg Andreas , Vollmayr Barbara , Kelsch Wolfgang , Sartorius Alexander
Published: April 2018

Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date. We combined optogenetics and functional magnetic resonance imaging (fMRI), to establish a causal relationship, using an animal model of treatment-resistant depression, namely Negative Cognitive State rats. First, an inhibitory light-sensitive ion channel was introduced into the LHb by viral transduction. Subsequently, laser stimulation was performed during fMRI acquisition on a 9.4 Tesla animal scanner. Neural activity and connectivity were assessed, before, during and after laser stimulation. We observed a connectivity decrease in the DMN following laser-induced LHb perturbation. Our data indicate a causal link between LHb downregulation and reduction in DMN connectivity. These findings may advance our mechanistic understanding of LHb inhibition, which had previously been identified as a promising therapeutic principle, especially for treatment-resistant depression.
Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome
Authors: Hou Hsin-An , Tsai Cheng-Hong , Lin Chien-Chin , Chou Wen-Chien , Kuo Yuan-Yeh , Liu Chieh-Yu , Tseng Mei-Hsuan , Peng Yen-Ling , Liu Ming-Chih , Liu Chia-Wen , Liao Xiu-Wen , Lin Liang-In , Yao Ming , Tang Jih-Luh , Tien Hwei-Fang
Published: April 2018

Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of CBL, IDH2, ASXL1, DNMT3A, and TP53 were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups (P < 0.001 for both OS and leukemia-free survival). In conclusion, integration of gene mutations in current IPSS-R improves the prognostication of MDS patients and may help identify high-risk patients for more aggressive treatment in IPSS-R lower risk group.