bluuebunny/crossref_metadata_2025 huggingface dataset:
Aminopyrine breath test predicts liver‐related events and death in HCV‐related cirrhosis on SVR after DAA therapy
Authors: Petta Salvatore , Rini Francesca , Calvaruso Vincenza , Cammà Calogero , Ciminnisi Stefania , Di Marco Vito , Giannini Edoardo G. , Grimaudo Stefania , Maria Pipitone Rosaria , Craxì Antonio
Published: September 2019

Background & Aims

In patients with hepatitis C virus (HCV)‐related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13C‐aminopyrine breath test (ABT) to assess whether its changes can predict liver‐related outcomes after DAA treatment in patients with HCV cirrhosis.

Methods

Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation – defined as Child A6 (N = 22, 44%) or previous decompensation (N = 7, 14%) – or Child B cirrhosis (N = 21, 42%) eligible for DAA‐based antiviral therapy. ABT was performed at baseline and 12 weeks after the end of antiviral therapy. Patients received sofosbuvir‐based regimens.

Results

Aminopyrine breath test was available for all 50 patients at baseline. The 120’ cumulative dose was directly associated at regression analysis only with albumin levels (P = .001). ABT was available at follow‐up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2 months (range 12.2‐32.1 months). Lower Ʌ ABT – defined as changes of 120’ cumulative dose from FUW12 to baseline – (HR 0.97, 95% CI 0.94‐0.99; P = .02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16‐310.3; P = .03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of Ʌ ABT was good (0.87, 95% CI 0.75‐0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver‐related events/death (P < .001).

Conclusions

In patients with advanced HCV cirrhosis who achieve SVR with DAA, Ʌ ABT assists in assessing the residual likelihood of liver‐related events and deaths after viral cure.
Impact of cultural diversity on local labor markets. Evidence from Greece's “age of mass migration”
Authors: Roupakias Stelios , Dimou Spiridoula
Published: September 2019

This paper analyzes how the interaction of ethnicities and cultures impacts on productivity and employment on Greek local labor markets, within the 20‐year interval between 1991 and 2011. We compute two alternative proxies for cultural diversity, namely the fractionalization and the polarization index, using information on 118 countries of origin. We also account for the potential endogenous allocation of individuals across local labor markets by employing a “shift‐share” instrument, exploiting the fact that networks play an important role in the settlement patterns of recent migrants. Our identification strategy indicates that the contribution of diversity in terms of birthplace is positive, at least up to a certain point. This finding appears to be robust and not driven by the inclusion of further controls, outliers, spatial autocorrelation, and selection on unobservables. Interestingly, we find that ethnic heterogeneity helps employment and productivity by promoting sectoral diversity.
Linking shock textures revealed by BSE, CL, and EBSD with U‐Pb data (LA‐ICP‐MS and SIMS) from zircon from the Araguainha impact structure, Brazil
Authors: Hauser Natalia , Reimold Wolf Uwe , Cavosie Aaron J. , Crósta Alvaro P. , Schwarz Winfried H. , Trieloff Mario , Da Silva Maia de Souza Carolinna , Pereira Luciana A. , Rodrigues Eduardo N. , Brown Matthews
Published: September 2019

A silicious impact melt rock from polymict impact breccia of the northern part of the alkali granite core of the Araguainha impact structure, central Brazil, has been investigated. The melt rock is thought to represent a large mass of impact‐generated melt in suevite. In particular, a diverse population of zircon grains, with different impact‐induced microstructures, has been analyzed for U‐Pb isotopic systematics. Backscattered electron and cathodoluminescence images reveal heterogeneous intragrain domains with vesicular, granular, vesicular plus granular, and vesicular plus (presumably) baddeleyite textures, among others. The small likely baddeleyite inclusions are not only preferentially located along grain margins but also occur locally within grain interiors. LA‐ICP‐MS U‐Pb data from different domains yield lower intercept ages of 220, 240, and 260 Ma, a result difficult to reconcile with the previous “best age” estimate for the impact event at 254.7 ± 2.7 Ma. SIMS U‐Pb data, too, show a relatively large range of ages from 245 to 262 Ma. A subset of granular grains that yielded concordant SIMS ages were analyzed for crystallographic orientation by EBSD. Orientation mapping shows that this population consists of approximately micrometer‐sized neoblasts that preserve systematic orientation evidence for the former presence of the high‐pressure polymorph reidite. In one partially granular grain (#36), the neoblasts occur in linear arrays that likely represent former reidite lamellae. Such grains are referred to as FRIGN zircon. The best estimate for the age of the Araguainha impact event from our data set from a previously not analyzed type of impact melt rock is based on concordant SIMS data from FRIGN zircon grains. This age is 251.5 ± 2.9 Ma (2σ, MSWD = 0.45, p = 0.50, n = 4 analyses on three grains), indistinguishable from previous estimates based on zircon and monazite from other impact melt lithologies at Araguainha. Our work provides a new example of how FRIGN zircon can be combined with in situ U‐Pb geochronology to extract an accurate age for an impact event.
Dual‐mycorrhizal plants: their ecology and relevance
Authors: Teste François P. , Jones Melanie D. , Dickie Ian A.
Published: September 2019

Dual‐mycorrhizal plants are capable of associating with fungi that form characteristic arbuscular mycorrhizal (AM) and ectomycorrhizal (EM) structures. Here, we address the following questions: (1) How many dual‐mycorrhizal plant species are there? (2) What are the advantages for a plant to host two, rather than one, mycorrhizal types? (3) Which factors can provoke shifts in mycorrhizal dominance (i.e. mycorrhizal switching)? We identify a large number (89 genera within 32 families) of confirmed dual‐mycorrhizal plants based on observing arbuscules or coils for AM status and Hartig net or similar structures for EM status within the same plant species. We then review the possible nutritional benefits and discuss the possible mechanisms leading to net costs and benefits. Cost and benefits of dual‐mycorrhizal status appear to be context dependent, particularly with respect to the life stage of the host plant. Mycorrhizal switching occurs under a wide range of abiotic and biotic factors, including soil moisture and nutrient status. The relevance of dual‐mycorrhizal plants in the ecological restoration of adverse sites where plants are not carbon limited is discussed. We conclude that dual‐mycorrhizal plants are underutilized in ecophysiological‐based experiments, yet are powerful model plant–fungal systems to better understand mycorrhizal symbioses without confounding host effects.
Equality as an ethical concept within the context of nursing care rationing
Authors: Papastavrou Evridiki , Igoumenidis Michael , Lemonidou Chryssoula
Published: September 2019

The concept of equality is subject to many different interpretations, and it is closely connected to similar concepts such as equity, justice, fairness, and human rights. As an ideal, equality entails many aspects that are untenable. For instance, genetic and social inequalities may never be extinct, but they can both be ameliorated by proper distribution of society's resources. Likewise, within the context of health care, equality can be promoted by proper rationing of health resources, amongst which nursing care stands out. In the field of nursing, the principle of equality presents itself in various forms of ethical and deontological mandates. However, beyond good intentions and abstract notions, there is a need to examine the ways in which nurses enforce this principle in practice, within the reality of modern health systems. Although there is scarcity of qualitative evidence in the nursing care rationing literature, existing studies suggest that fair treatment pertains to a largely intuitive sense of equality which involves subjective perceptions and judgements about rationing. Nurses’ initial predisposition is to view all patients as equal and treat them in an equal manner; yet, on an individual basis, each patient has a different starting point, different needs and different prospects that render rationing decisions complex and uncertain. Equality should be accepted with its unavoidable limitations in practice and be further examined within the context of nursing care rationing, in the hope that it can be advanced in a consistent way, despite the idealistic nature in many of its aspects.
Optimum waist circumference‐height indices for evaluating adult adiposity: An analytic review
Authors: Hwaung Phoenix , Heo Moonseong , Kennedy Samantha , Hong Sangmo , Thomas Diana M. , Shepherd John , Heymsfield Steven B.
Published: September 2019

Phenotyping adults for excess adiposity and related health risks usually include three body size measurements: height, weight and waist circumference (WC). Height and weight are now widely used as components of the body shape measure, body mass index (BMI, weight/height2), with the height power referred to as the scaling factor, α. At present, WC is usually not adjusted for height or is expressed as WC/height in which α = 1. Although other α values have been proposed, a critical review of these shape measures is lacking. Here, we examine classical pathways by which the scaling exponent for height used in BMI was developed and then apply this strategy to identify the optimum WC index characteristic of adult shape. Our analyses explored anthropometric, body composition and clinically‐relevant data from US and Korean National Health and Nutrition Surveys. Our findings provide further support for the WC index of WC/height0.5 as having the strongest associations with adiposity while having the weakest correlations with height across non‐Hispanic white and black, Mexican American and Korean men and women. The WC index, defined as WC/height0.5, when combined with BMI, can play an important role when phenotyping adults for excess adiposity and associated health risks in research and clinical settings.
Teaching Genuine Dialogue: The Potential for Using Improv
Authors: O'Neal Kathleen , Hastings Sally O.
Published: September 2019

Scholars proclaim the potential for genuine dialogue to reduce conflict and promote more harmonious interpersonal interactions. Despite dialogue's usefulness, little guidance has been given regarding helping students to improve their likelihood of reaping the benefits of genuine dialogue. Focus groups were conducted with students of theatrical improvization (improv) courses to learn what kinds of dialogic skills they acquire from their improv experience. Thematic analysis was used to learn what improv students were learning that demonstrated consistency with characteristics of dialogue. Analysis revealed that their training in improv fostered: Imagination and Innovation, Vulnerability, and Immediacy of Presence. The analysis considers the dialogic quality least effectively articulated among participants—empathy—and explores the relevance of the findings for promoting dialogue through classroom inquiry.
Sleep quality is associated with psychosocial functioning and health‐related quality of life in pediatric transplant recipients
Authors: Gutierrez‐Colina Ana M. , Quast Lauren F. , Eaton Cyd K. , LaMotte Julia , Stolz Mary G. , Mee Laura , George Roshan , Lee Jennifer , Reed Bonney , Rich Kristin Loiselle , Blount Ronald L.
Published: September 2019

This study examined patient‐reported sleep quality in a single‐center cross‐sectional sample of adolescents with solid organ transplants and evaluated associations between sleep quality, psychosocial functioning (ie, depression/anxiety symptoms), and HRQOL. Health disparities associated with minority race/ethnicity and socioeconomic variables were also examined. Sixty‐nine adolescents (M = 16.51 years; SD = 1.63) who received a solid organ transplant (kidney: n = 25; liver: n = 24; heart: n = 20) completed self‐report measures of sleep quality, psychosocial functioning, and HRQOL. Adolescent transplant recipients endorsed significantly lower levels of sleep quality (ie, falling asleep) compared with previously published norms of healthy peers (t = −3.60; P ≤ .001). Higher sleep quality was significantly associated with fewer anxiety and depressive symptoms (r = −.31 to −.40), and higher physical and psychosocial HRQOL (r = .33‐.43). Adolescents from minority backgrounds had significantly worse sleep quality compared with non‐Hispanic Whites. Adolescent transplant recipients, particularly those from minority backgrounds, may be at increased risk for experiencing poor sleep quality. Suboptimal sleep is a risk factor for higher levels of anxiety and depressive symptoms, as well as lower levels of physical and psychosocial HRQOL. Sleep is an important modifiable factor that, if improved, may contribute to lower anxiety/depressive symptoms and better HRQOL in adolescent transplant recipients.
Analysis of Internet searches using Google Trends to measure interest in sun protection and skin cancer in selected South‐East Asian populations
Authors: Kwan Zhenli , Yong Shin Shen , Robinson Suganthy
Published: September 2019

Background

Analysis of Internet search trends has been performed to evaluate interest in sun protection, artificial tanning, and skin cancers among the public, particularly in Western countries. This observational study aimed to investigate the relative popularity of search terms relating to sun protection, sunburn, skin cancers, and tanning used in Google Trends® in three South‐East Asian countries (Malaysia, Singapore, and Indonesia).

Methods

The relevant search terms were queried using the Google Trends® in each location and worldwide. The search volume indices were compared between locations and over a time period from January 1, 2004, to January 31, 2019. Correlations between “sunblock” and “sunburn” as well as “sunblock” and search terms relating to skin cancers (“skin cancer,” “melanoma,” “basal cell carcinoma,” and “squamous cell carcinoma”) were evaluated.

Results

The favored search term relating to sun protection in this region was “sunblock” despite the term itself being a misnomer. The relative popularity of searches for “sunblock” also showed an increase over time and was generally higher compared with interest in sunburn, skin cancers, and artificial tanning practices. Positive correlations were noted between “sunblock” and “sunburn” in Malaysia and “sunblock” and “melanoma” in Singapore.

Conclusion

Insights into search trends may assist public health promotion to raise awareness regarding sun protection and skin cancers in the region by targeting commonly used terms for each geographical location.
Modal Security
Authors: Clarke‐Doane Justin , Baras Dan
Published: September 2019

Modal Security is a proposed necessary condition for undermining defeat. It has been widely discussed of late. The principal is of interest because it seems to entail that influential epistemological arguments, including Evolutionary Debunking Arguments against moral realism and the Benacerraf‐Field Challenge for mathematical realism, are unsound. Modal Security says, roughly, that if evidence undermines (rather than rebuts) one’s belief, then one gets reason to doubt the belief’s safety or sensitivity. The purpose of this paper is to critically examine Modal Security in detail. We begin by presenting the principle and its motivations as well as the role it plays in the debunking arguments debate. We then develop and discuss what we take to be the strongest objections to the principle, and see what can be said in response. Six such arguments, as well as a worry that epistemic justification requires a “connection” between the beliefs and the facts, are developed, discussed and criticized. The article reveals how the debate surrounding Modal Security interacts with core problems in epistemology—including the generality problem and the distinction between direct and indirect evidence.
Cerebral arterial air emboli after stent insertion in esophageal cancer complicated with esophago‐left atrial fistula: An autopsy case and review of the literature
Authors: Park Jong Kun , Goto Takayoshi , Nagano Teruaki , Yoshimura Michiko , Yutani Chikao
Published: September 2019

Cerebral arterial air embolism is a rare and unexpected complication of advanced esophageal cancer. The entry of air to systemic circulation is an esophago‐left atrial or pulmonary vein fistula formation. Herein, we report an autopsy case of a 64‐year‐old man. He was diagnosed esophageal cancer 2 years ago and underwent chemotherapy and concurrent chemoradiotherapy but the disease progressed, unfortunately. Then two metal stents were inserted into the middle thoracic esophagus as a palliation of dysphagia. After initiation of oral intake, he developed deterioration of consciousness. The cranial computed tomography showed cerebral arterial air emboli with multiple low‐density areas. He failed to gain consciousness again and died one and half days later. In a literature survey, this autopsy case is the first presentation that confirmed histologically the close association between stent placement and formation of esophago‐left atrial fistula. Due to the fatality of cerebral arterial air embolism, clinicians should keep in mind the possibility of this catastrophic complication after multimodality treatment of esophageal cancer.
Mechanisms of nuclear mRNA export: A structural perspective
Authors: Xie Yihu , Ren Yi
Published: September 2019

Export of mRNA from the nucleus to the cytoplasm is a critical process for all eukaryotic gene expression. As mRNA is synthesized, it is packaged with a myriad of RNA‐binding proteins to form ribonucleoprotein particles (mRNPs). For each step in the processes of maturation and export, mRNPs must have the correct complement of proteins. Much of the mRNA export pathway revolves around the heterodimeric export receptor yeast Mex67•Mtr2/human NXF1•NXT1, which is recruited to signal the completion of nuclear mRNP assembly, mediates mRNP targeting/translocation through the nuclear pore complex (NPC), and is displaced at the cytoplasmic side of the NPC to release the mRNP into the cytoplasm. Directionality of the transport is governed by at least two DEAD‐box ATPases, yeast Sub2/human UAP56 in the nucleus and yeast Dbp5/human DDX19 at the cytoplasmic side of the NPC, which respectively mediate the association and dissociation of Mex67•Mtr2/NXF1•NXT1 onto the mRNP. Here we review recent progress from structural studies of key constituents in different steps of nuclear mRNA export. These findings have laid the foundation for further studies to obtain a comprehensive mechanistic view of the mRNA export pathway.
CT variants of the caudal vena cava in 121 small breed dogs
Authors: Ryu Chanyoung , Choi Sooyoung , Choi Hojung , Lee Youngwon , Lee Kija
Published: September 2019

Computed tomography is increasingly used as a treatment planning method in canine patients with diseases of the retroperitoneum, however, published information on normal variations in the caudal vena cava (CVC) are currently lacking. The objectives of this retrospective descriptive study were to characterize CVC variants using CT angiography in a sample of small breed dogs and localize the CVC bifurcations for each variant. Inclusion criteria were small breed dogs (weight ≤ 15) that underwent contrast‐enhanced CT scans of the CVC, abdominal aorta, and CVC tributaries. A total of 121 small breed dogs were sampled. Four right‐sided and one left‐sided CVC variations were identified: normal (88/121, 72.7%), caudal‐partial split (17/121, 14.0%), partial duplication (8/121, 6.6%), complete duplication (7/121, 5.8%), and left‐sidedness (1/121, 0.8%). The mean lumbar vertebral levels of the CVC bifurcation were L6.39 ± 0.41, L5.70 ± 0.35, L4.39 ± 0.42, L2.74 ± 0.38, and L6.4 in the normal, caudal‐partial split, partial duplication, complete duplication, and left‐sidedness types, respectively. The location of the CVC bifurcation, the relationship between the aortic trifurcation and the CVC bifurcation, and the location of the bilateral deep circumflex iliac veins with respect to the CVC bifurcation were significantly different among the right‐sided types (P ≤ .001). Bilateral deep circumflex iliac veins joined to the ipsilateral common iliac veins and the CVC in the caudal‐partial split and duplication types, respectively. The results of this study indicated that canine CVC variants may be frequent and should be considered during surgery or diagnostic imaging of the retroperitoneum.
Design and Testing of a Miniaturized Five-Hole Fast Response Pressure Probe With Large Frequency Bandwidth and High Angular Sensitivity
Authors: Boufidi Elissavet , Alati Marco , Fontaneto Fabrizio , Lavagnoli Sergio
Published: September 2019

A miniaturized five-hole fast response pressure probe is presented, and the methods for the aerodynamic design and performance characterization are explained in detail. The probe design is aimed for three-dimensional (3D) time-resolved measurements in turbomachinery flows, therefore requiring high frequency response and directional sensitivity. It features five encapsulated piezoresistive pressure transducers, recessed inside the probe hemispherical head. Theoretical and numerical analyses are carried out to estimate the dynamic response of the pressure tap line-cavity systems and to investigate unsteady effects that can influence the pressure readings. A prototype is manufactured and submitted to experimental tests that demonstrate performance in line with the theoretical and numerical predictions of the dynamic response: the natural frequency of the central and lateral taps extends to 200 and 25 kHz, respectively. An aerodynamic calibration is also performed at different Reynolds and Mach numbers. The probe geometry offers a good angular sensitivity in a ± 30 deg incidence range, while a frequency analysis reveals the presence of pressure oscillations related to vortex shedding at large angles of attack.
Statistical Modal Analysis for Out-of-Plane Deviation Prediction in Additive Manufacturing Based on Finite Element Simulation
Authors: Zhu Zuowei , Anwer Nabil , Mathieu Luc
Published: September 2019

Despite the rapid growth and widespread recognition of additive manufacturing (AM) technologies, the geometrical inaccuracy of the manufactured products remains a challenging issue and effective prediction of the geometric deviations in AM is critical for the solution of this issue. The layerwise characteristic of the AM process has motivated the investigation of deviation from in-plane and out-of-plane perspectives, the latter has been seldom studied and will be the focus of this paper. In this paper, an out-of-plane deviation modeling method will be proposed based on statistical modal analysis. Owing to the inconvenience in data acquisition, AM simulation is conducted to obtain the layer-level out-of-plane deviation on parts manufactured by the selective laser melting process. Discrete cosine transform is adopted to identify the major deviation modes from the data. The statistical relationship between mode coefficients and related part and process parameters is studied based on the Gaussian process model. To gain data for model training, experimental design is conducted to sample parameter combinations as simulation input. A case study is presented to demonstrate the proposed method and the effectiveness is validated on test data. The method can be applied in multiple domains of AM, such as quality control and tolerancing, to provide high-fidelity prediction of geometric deviations.
On the Mechanism of Bandgap Formation in Beams With Periodic Arrangement of Beam-Like Resonators
Authors: Serrano Ó. , Zaera R. , Fernández-Sáez J.
Published: September 2019

Metastructures made of spring-mass resonators present a bandgap at the natural frequency of the resonator. This rule cannot be generalized for more complex resonators. This work analyzes the case of a metastructure composed of a periodic arrangement of vertical beams rigidly joined to a horizontal beam. The vertical beams work as resonators, and their natural frequencies play a strong role on the band structure of the whole system, however, different than the case with spring-mass resonators. Since this metastructure can be considered a lattice, Bloch’s theorem is applied to the unit cell and a numerical procedure based on the finite element method permits to obtain the dispersion curves. Illustrative results show the influence of the natural frequencies of the horizontal and vertical beams on the band structure.
Effect of Bulkhead Pressurization on the Vibro-Acoustic Properties of an Aft-Fuselage-Mounted Twin-Engine Aircraft
Authors: Warwick Braden T. , Mechefske Chris K. , Kim Il Yong
Published: September 2019

Despite widespread use of an aft-fuselage-mounted twin-engine aircraft in the business jet industry, a thorough investigation into the vibro-acoustic properties of this aircraft type has yet to be undertaken. Additionally, the effect of bulkhead pressurization on the vibro-acoustic properties of this aircraft fuselage has yet to be investigated in isolation. This work investigates the effect of bulkhead pressurization on two different designs of an aft-fuselage-mounted twin-engine aircraft: a single and a double bulkhead designs. A modal analysis, a harmonic frequency response analysis, and an acoustic response analysis were performed. A split bulkhead pressurization methodology was introduced as a means of improving structural performance without impacting passenger comfort levels in a double bulkhead aircraft. Modal coupling between components was seen to be the primary cause of increased cabin noise, peaking above 80 Hz. The bulkhead frequency response was highly dependent upon bulkhead pressurization, as the modal participation factors were significantly impacted by bulkhead pressurization. Therefore, the importance of understanding all bulkhead natural frequencies was highlighted, as the response changed as a function of bulkhead pressurization. Bulkhead resonance conditions generated a tone in the acoustic frequency response inside the passenger cabin, highlighting the importance of this component to passenger comfort levels.
Experimental and analytical evaluation of the acoustic radiation of femtosecond laser plasma filament sound sources in air
Authors: Kaleris Konstantinos , Orfanos Yannis , Bakarezos Makis , Papadogiannis Nektarios , Mourjopoulos John
Published: September 2019

Plasma filaments in air induced by femtosecond laser pulses lead to the generation of strong shock waves. This letter presents a systematic study, both experimental and theoretical, of the acoustic radiation by femtosecond laser-generated filaments. A theoretical model is developed based on the experimental results and is used to evaluate the directivity of the filament's acoustic radiation within and beyond the audible frequency range. It is shown that the acoustic directivity of plasma filaments can be derived from the model of a weighted acoustic line source, consisting of elementary point sources with N-shaped excitation.
Response to Comment on “A commensal strain of
Staphylococcus epidermidis
protects against skin neoplasia” by Nakatsuji
et al
.
Authors: Nakatsuji Teruaki , Fenical William , Gallo Richard L.
Published: September 2019

Common strains of
Staphylococcus epidermidis
on the human skin inhibit UV-induced neoplasia without adverse effects.
Mitoribosomal small subunit biogenesis in trypanosomes involves an extensive assembly machinery
Authors: Saurer Martin , Ramrath David J. F. , Niemann Moritz , Calderaro Salvatore , Prange Céline , Mattei Simone , Scaiola Alain , Leitner Alexander , Bieri Philipp , Horn Elke K. , Leibundgut Marc , Boehringer Daniel , Schneider André , Ban Nenad
Published: September 2019

Assembly pathway for mitoribosome

The biogenesis of ribosomes is a multistep process facilitated by assembly factors. Saurer
et al.
provided structural information on the maturation process of the mitochondrial ribosome, or mitoribosome, in the parasitic protozoan
Trypanosoma brucei
(see the Perspective by Karbstein). Cells evolved a dedicated machinery for maturation of the small subunit of the mitoribosome, including the formation of three distinct and well-structured assembly intermediates. Comparison of intermediates and the mature mitoribosome reveals how assembly factors and ribosomal proteins work together to fold and stabilize ribosomal RNA.

Science
, this issue p.
1144
; see also p.
1077
A neonicotinoid insecticide reduces fueling and delays migration in songbirds
Authors: Eng Margaret L. , Stutchbury Bridget J. M. , Morrissey Christy A.
Published: September 2019

Hazardous delays

Neonicotinoids are a widely used group of pesticides that have been shown to have negative impacts on an increasing number of species, most notably pollinators. Eng
et al.
tested how exposure to these compounds influenced the behavior of a migrating songbird. Ingestion of field-realistic levels of neonicotinoid insecticides reduced feeding and accumulation of body mass and fat stores, which led to delayed departure from stopover sites. Such delays can lead to reduced migration survival and decreased reproductive success and therefore have the potential to impose population-level impacts.

Science
, this issue p.
1177
Humboldt’s enigma: What causes global patterns of mountain biodiversity?
Authors: Rahbek Carsten , Borregaard Michael K. , Colwell Robert K. , Dalsgaard Bo , Holt Ben G. , Morueta-Holme Naia , Nogues-Bravo David , Whittaker Robert J. , Fjeldså Jon
Published: September 2019

Mountains contribute disproportionately to the terrestrial biodiversity of Earth, especially in the tropics, where they host hotspots of extraordinary and puzzling richness. With about 25% of all land area, mountain regions are home to more than 85% of the world’s species of amphibians, birds, and mammals, many entirely restricted to mountains. Biodiversity varies markedly among these regions. Together with the extreme species richness of some tropical mountains, this variation has proven challenging to explain under traditional climatic hypotheses. However, the complex climatic characteristics of rugged mountain regions differ fundamentally from those of lowland regions, likely playing a key role in generating and maintaining diversity. With ongoing global changes in climate and land use, the role of mountains as refugia for biodiversity may well come under threat.
An optical tweezer array of ultracold molecules
Authors: Anderegg Loïc , Cheuk Lawrence W. , Bao Yicheng , Burchesky Sean , Ketterle Wolfgang , Ni Kang-Kuen , Doyle John M.
Published: September 2019

Tweezing cold molecules

Arrays of optical tweezers have been used to trap atoms, but trapping and laser-cooling molecules in this setting is tricky. Such an approach would, however, be generalizable to many molecular species. Anderegg
et al.
created an optical tweezer array of calcium monofluoride molecules, which were laser cooled to their ground state (see the Perspective by Kotochigova). By distinguishing between single and multiple molecules in the tweezers, the researchers were able to observe molecular collisions. Boasting exquisite control over individual molecules, the optical tweezer array platform holds much promise for extending the applications of ultracold molecules.

Science
, this issue p.
1156
; see also p.
1079
Seconds-scale coherence on an optical clock transition in a tweezer array
Authors: Norcia Matthew A. , Young Aaron W. , Eckner William J. , Oelker Eric , Ye Jun , Kaufman Adam M.
Published: September 2019

Building up an optical clock

Arrays of optical tweezers can be used to trap atoms, which can then be manipulated individually. Such arrays have shown promise in quantum simulation of many-body systems. Norcia
et al.
now demonstrate that they can also be used as a platform for optical clocks. The researchers lined up 10 optical tweezers in a one-dimensional array, where each tweezer held either one or zero atoms of strontium. The atoms were subjected to laser light whose frequency was tuned to a clock transition in strontium. By monitoring the number of atoms in each tweezer, the researchers measured a long coherence time of a few seconds. Increasing the number of tweezers should improve the figures of merit of this platform.

Science
, this issue p.
93
Viruses teach T cells to tackle tumors
Authors: Hickman Heather D.
Published: September 2019

Oncolytic vaccinia virus expressing leptin enhances T cell clearance of melanomas.
Ammonia Oxidizers in High-Elevation Rivers of the Qinghai-Tibet Plateau Display Distinctive Distribution Patterns
Authors: Zhang Sibo , Xia Xinghui , Li Siling , Zhang Liwei , Wang Gongqin , Li Meishui , Shi Yinan , Chen Nengwang
Published: September 2019

Ammonia-oxidizing archaea (AOA) and bacteria (AOB) as well as comammox contribute to ammonia oxidation, which plays significant roles in riverine nitrogen cycle and N
2
O production. Source regions of numerous rivers in the world lie in high-elevation zones, but the abundance, community, and activity of ammonia oxidizers in rivers in high-elevation regions have rarely been investigated. This study revealed distinctive distribution patterns and community structures for ammonia oxidizers in five high-elevation rivers of the Qinghai-Tibet Plateau, and the individual and combined effects of low temperature, low nutrients, and strong solar radiation on ammonia oxidizers were elucidated. The findings of this study are helpful to broaden our knowledge on the biogeography and distribution pattern of ammonia oxidizers in river systems. Moreover, this study provides some implications to predict the performance of ammonia oxidizers in high-elevation rivers and its variations under global climate warming.
Wastewater as a Probable Environmental Reservoir of Extended-Spectrum-β-Lactamase Genes: Detection of Chimeric β-Lactamases CTX-M-64 and CTX-M-123
Authors: Tanaka Hayato , Hayashi Wataru , Iimura Masaki , Taniguchi Yui , Soga Eiji , Matsuo Nao , Kawamura Kumiko , Arakawa Yoshichika , Nagano Yukiko , Nagano Noriyuki
Published: September 2019

Global spread of CTX-M-type extended-spectrum β-lactamase (ESBL)-producing
Enterobacteriaceae
is a critical concern in both clinical and community settings. This dominance of CTX-M-type ESBL producers may be largely due to the successful international spread of epidemic clones, as represented by the extraintestinal pathogenic
Escherichia coli
(ExPEC) ST131. Our findings highlight the worrisome presence of diverse
E. coli
clones associated with humans, including ExPEC lineages harboring the most common
bla
CTX-M
variants in untreated wastewater samples. Moreover, the chimeric genes
bla
CTX-M-64
and
bla
CTX-M-123
, which have not yet been identified from human isolates of domestic origin in Japan, were identified. Exposure to untreated wastewater through combined sewer overflow caused by heavy rains derived from abnormal weather change could pose a risk for human health due to ingesting those antimicrobial-resistant bacteria.
Complete Genome Sequences of Brenneria rubrifaciens Strain 6D370 and Brenneria nigrifluens Strain ATCC 13028, Causative Agents of Bark Cankers in Walnut
Authors: Poret-Peterson Amisha T. , McClean Ali E. , Chen Limin , Kluepfel Daniel A.
Published: September 2019

Brenneria rubrifaciens
and
Brenneria nigrifluens
, respectively, cause deep and shallow bark canker disease in walnut.
B. rubrifaciens
exhibits quorum sensing-controlled virulence and rubrifacine pigment production. The complete genome sequences of these species will be useful for studying the role of genes regulated by quorum sensing, including pathways mediating pathogenesis.
Genome Sequences of 17 Pasteurella multocida Strains Involved in Cases of Rabbit Pasteurellosis
Authors: Kempf Florent , Chambellon Emilie , Helloin Emmanuelle , Garreau Hervé , Lantier Frédéric
Published: September 2019

This article reports draft genome sequences of 17
Pasteurella multocida
strains isolated from naturally infected rabbits. The total lengths of the assembled contigs ranged between 2.21 and 2.48 Mb, and the total number of genes detected on the contigs ranged between 2,088 and 2,416.
Draft Genome Sequence of Novel
Metschnikowia
sp. Strain JCM 33374, a Nectar Yeast Isolated from a Bumblebee
Authors: Hirao Akira S. , Imai Ryosuke , Endoh Rikiya , Ohkuma Moriya , Degawa Yousuke
Published: September 2019

Here, we report the draft genome sequence of
Metschnikowia
sp. strain JCM 33374, a nectar yeast isolated from a bumblebee (
Bombus diversus
). The genome of 20.1 Mb is a naturally heterozygous diploid. Phylogenetic analysis with related taxa demonstrated that the strain is very likely a novel species.
Complete Genome Sequencing of a Novel Strain of Sapelovirus A Circulating in Vietnam
Authors: Dang Hoang Vu , Kato Tomoko , Nishi Tatsuya , Tran Ha Thanh , Miyazawa Kohtaro , Kokuho Takehiro
Published: September 2019

Sapelovirus A (SV-A) is currently spreading as an enteric pathogen of pigs worldwide. We isolated SV-A strain XTND/2018 from the small intestine of a dead pig with severe diarrhea in the north of Vietnam and determined the genomic sequence. This is the first report of the genomic sequence of SV-A circulating in Vietnam.
Ziv-aflibercept combined with intravitreal steroid for management of peripheral exudative haemorrhagic chorioretinopathy
Authors: Balakrishnan Divya , Oli Avadhesh
Published: September 2019

Peripheral exudative haemorrhagic chorioretinopathy (PEHCR) is considered a variant of polypoidal choroidal vasculopathy. It may have varried presentations and systemic associations. We present a case of PEHCR which dramatically responded to intravitreal steroid and ziv-aflibercept injection. This case not only highlights the promising role of combination therapy with intravitreal steroids and ziv-aflibercept but also the need to look for any associated systemic comorbidity.
Insulin price components: case studies in six low/middle-income countries
Authors: Ball Douglas , Ewen Margaret , Laing Richard , Beran David
Published: September 2019

Introduction

Understanding price components for insulin products can help design interventions to improve insulin affordability in low/middle-income countries.

Methods

An adapted WHO/Health Action International standardised methodology was used in Brazil (Rio de Janeiro), China (Hubei and Shaanxi Provinces), Ghana, India (Haryana State), Indonesia and Uganda. Selected insulin products had their prices traced backwards through the supply chain from public and private sector retail outlets in the capital city and a district town, supplemented with key informant interviews.

Results

Cumulative mark-ups ranged from 8.7% to 565.8% but the magnitude of mark-ups was country specific and variable within and across sectors and regions. The proportion of the patient price attributed to the manufacturer’s selling price varied from 15.0% to 92.0%. Pricing regulations in China, India and Indonesia reduced wholesale and retail mark-ups but did not guarantee low prices. Most countries had removed import duties (Ghana, India, Indonesia, Uganda), but additional tariffs of 3.5% were still applied in Ghana. Value-added tax in the private sector ranged from 5% to 20% across the countries.

Conclusion

There are no clear trends in the mark-ups applied to insulin or specific differences in the price structure. A uniform approach to improving insulin access through regulating price components is unlikely to be successful, but elimination of duties and taxes, price regulation and greater price transparency could help influence prices and hence affordability.
Injection therapy for base of thumb osteoarthritis: a systematic review and meta-analysis
Authors: Riley Nicholas , Vella-Baldacchino Martinique , Thurley Neal , Hopewell Sally , Carr Andrew J , Dean Benjamin John Floyd
Published: September 2019

Objective

To evaluate the effectiveness of injection-based therapy in base of thumb osteoarthritis.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO were searched from inception to 22 May 2018.

Study selection

Randomised controlled trials (RCTs) and non-RCTs of adults with base of thumb osteoarthritis investigating an injection-based intervention with any comparator/s.

Data extraction and analysis

Data were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were pain and function. Comparative treatment effects were analysed by random-effects model for short-term and medium-term follow-up.

Results

In total, 9 RCTs involving 504 patients were identified for inclusion. All compared different injection-based therapies with each other, no studies compared an injection-based therapy with a non-injection-based intervention. Twenty injection-based intervention groups were present within these nine trials, consisting of hyaluronic acid (n=9), corticosteroid (n=7), saline placebo (n=3) and dextrose (n=1). Limited meta-analysis was possible due to the heterogeneity in the injections and outcomes used, as well as incomplete outcome data. Meta-analysis of two RCTs (92 patients) demonstrated reduced Visual Analogue Scale pain on activity with corticosteroid versus hyaluronic acid (mean difference (MD) −1.32, 95% CI −2.23 to −0.41) in the medium term, but no differences in other measures of pain or function in the short term and medium term. Overall, the available evidence does not suggest that any of the commonly used injection therapies are superior to placebo, one another or a non-injection-based comparator.

Conclusion

Current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis, both in terms of which injection-based therapy is the most effective and in terms of whether any injection-based therapy is more effective than other non-injection-based interventions. Given limited understanding of both the short-term and long-term effects, there is a need for a large, methodologically robust RCT investigating the commonly used injection therapies and comparing them with other therapeutic options and placebo.

PROSPERO registration number

CRD42018095384.
Trends in the association of different forms of precarious employment and self-rated health in Germany. An analysis with the German Socio-Economic Panel between 1995 and 2015
Authors: Pförtner Timo-Kolja , Pfaff Holger , Hower Kira Isabel
Published: September 2019

Background

Precarious employment has increased in Germany by means of labour market flexibilisation throughout the 1990s and 2000s. In this study, trends in the association of self-rated health (SRH) with different dimensions of precarious employment by gender in Germany between 1995 and 2015 were assessed considering different periods of labour market reforms and the Great Recession.

Methods

Analyses were conducted using the German Socio-Economic Panel from 1995 to 2015. All employed individuals aged 18–67 years and living in private households were considered for analysis to examine the risks of poor SRH by low wage, working poverty, non-standard working time arrangements and perceived job insecurity by gender. Predicted probabilities, adjusted risk ratio (ARR), adjusted risk difference (ARD) and trends were examined using pooled interval logistic regression with individual-clustered standard errors.

Results

Relative and absolute differences in SRH rose significantly over time by perceived job insecurity for men, but not for women. Working poverty appeared to be significantly associated with SRH in the Great Recession and the post-Recession period for both gender. Non-standard working time arrangements were not significantly associated with SRH for both gender, and low wage appeared to be significantly associated with SRH only for men in the post-Recession period.

Conclusions

The results highlighted the relevance of labour market reforms of deregulation and flexibilisation in Germany to differences in SRH by specific forms of precarious employment and gender differences in the impact of labour market reforms on precarious employment and health.
Elevated TIM3 expression of T helper cells affects immune system in patients with myelodysplastic syndrome
Authors: Fu Rong , Li Lijuan , Hu Jiaxin , Wang Yingshuai , Tao Jinglian , Liu Hui , Liu Zhaoyun , Zhang Wei
Published: September 2019

T cell immunoglobulin and mucin domain 3 (TIM3) expression is associated with immunosuppression and clinical outcomes in many diseases. However, the specific mechanism of TIM3 in immune system has not been clarified. In order to illustrate the mechanism of TIM3 in immune system, we analyzed the expression, function and regulation of TIM3 in T helper (Th)1 cells, Th2 cells, Th17 cells and regulatory T cells (Treg) through flow cytometry in patients with myelodysplastic syndrom (MDS). Our data showed elevated proportion of Th2 and Treg cells, while the proportion of Th1 and Th17 cells decreased in patients with MDS (p<0.05) and the expression of TIM3 increased in Th1, Th17 and Treg cells in patients with MDS when compared with expression in control patients (p<0.05). The secretion of transforming growth factor-β in TIM3+Treg cells decreased in patients with MDS. These findings suggested that TIM3 might affect immune helper systems by regulating Treg cells and related immune cells. Therefore, studying the role of the TIM3 pathway in MDS is necessary and may help to provide a new way to explore the pathogenesis and treatments of MDS.
Distal hereditary motor neuronopathy of the Jerash type is caused by a novel SIGMAR1 c.500A>T missense mutation
Authors: Ververis Antonis , Dajani Rana , Koutsou Pantelitsa , Aloqaily Ahmad , Nelson-Williams Carol , Loring Erin , Arafat Ala , Mubaidin Ammar Fayez , Horany Khalid , Bader Mai B , Al-Baho Yaqoub , Ali Bushra , Muhtaseb Abdurrahman , DeSpenza Jr Tyrone , Al-Qudah Abdelkarim A , Middleton Lefkos T , Zamba-Papanicolaou Eleni , Lifton Richard , Christodoulou Kyproula
Published: September 2019

Background

Distal hereditary motor neuronopathies (dHMN) are a group of genetic disorders characterised by motor neuron degeneration leading to muscle weakness that are caused by mutations in various genes. HMNJ is a distinct form of the disease that has been identified in patients from the Jerash region of Jordan. Our aim was to identify and characterise the genetic cause of HMNJ.

Methods

We used whole exome and Sanger sequencing to identify a novel genetic variant associated with the disease and then carried out immunoblot, immunofluorescence and apoptosis assays to extract functional data and clarify the effect of this novel SIGMAR1 mutation. Physical and neurological examinations were performed on selected patients and unaffected individuals in order to re-evaluate clinical status of patients 20 years after the initial description of HMNJ as well as to evaluate new and previously undescribed patients with HMNJ.

Results

A homozygous missense mutation (c.500A>T, N167I) in exon 4 of the SIGMAR1 gene was identified, cosegregating with HMNJ in the 27 patients from 7 previously described consanguineous families and 3 newly ascertained patients. The mutant SIGMAR1 exhibits reduced expression, altered subcellular distribution and elevates cell death when expressed.

Conclusion

In conclusion, the homozygous SIGMAR1 c.500A>T mutation causes dHMN of the Jerash type, possibly due to a significant drop of protein levels. This finding is in agreement with other SIGMAR1 mutations that have been associated with autosomal recessive dHMN with pyramidal signs; thus, our findings further support that SIGMAR1 be added to the dHMN genes diagnostic panel.