bluuebunny/crossref_metadata_2025 huggingface dataset:
c‐Myb promotes growth and metastasis of colorectal cancer through c‐fos‐induced epithelial‐mesenchymal transition
Authors: Qu Xiao , Yan Xuebing , Kong Cheng , Zhu Yin , Li Hao , Pan Dengdeng , Zhang Xiaohui , Liu Yongqiang , Yin Fang , Qin Huanlong
Published: July 2019

c‐Myb is a crucial transcription factor that participates in various biological functions; however, its role in colorectal cancer (CRC) remains poorly investigated. We first analyzed the expression and clinical significance of c‐Myb in a retrospective cohort enrolling 132 CRC patients. Then, the CRISPR/Cas9 technique was used to establish c‐Myb gene KO CRC cell lines. Cellular functional assays in vitro and in vivo were used to evaluate the impact of c‐Myb KO in CRC cells. Finally, RNA sequencing was used to investigate the potential oncogenic mechanisms regulated by c‐Myb in CRC progression and related cellular validations were accordingly carried out. As a result, c‐Myb is significantly overexpressed in CRC tissues as compared with adjacent normal tissues. High expression of c‐Myb is positively correlated with lymph node metastasis and poor prognosis. Univariate analysis and multivariate analysis further identify c‐Myb as an independent unfavorable prognostic factor for CRC patients. c‐Myb KO inhibits the proliferation, apoptosis resistance, invasion, metastasis, colony formation and in vivo tumorigenesis of CRC cells. Also, the mechanism investigation indicates that c‐Myb may promote CRC progression by regulating c‐fos. c‐fos overexpression can rescue the inhibitory effect of c‐Myb KO on the malignant characteristics of CRC cells. Finally, we find that c‐Myb KO inhibits the epithelial‐mesenchymal transition (EMT) molecular phenotype in CRC cells, whereas c‐fos overexpression can rescue this inhibitory effect. This study suggests that c‐Myb promotes the malignant progression of CRC through c‐fos‐induced EMT and has the potential to be a promising prognostic biomarker and therapeutic target.
End of the line for the golden lion tamarin? A single road threatens 30 years of conservation efforts
Authors: Ascensão Fernando , Niebuhr Bernardo B. , Moraes Andreia M. , Alexandre Brenda R. , Assis Julia C. , Alves‐Eigenheer Milene A. , Ribeiro John W. , de Morais Marcio M. , Martins Andreia F. , de Oliveira Ademilson , Moraes Elisamã , Ramos Jadir H. , Lorini Maria L. , Ferraz Luís P. , Culot Laurence , Dietz James M. , Ruiz‐Miranda Carlos R. , Ribeiro Milton C.
Published: July 2019

Roads have a myriad of negative effects on biodiversity, ultimately threatening the persistence of populations. In this Perspective we call attention to an extreme example, where the entire current geographic range of the endangered golden lion tamarin (Leontopithecus rosalia, GLT) is bisected by a major highway that is being widened to four lanes. We believe that the planned mitigation actions are not enough to reduce the expected increase of barrier effects and road mortality. These impacts may lead to a sequence of cascading effects that could jeopardize the conservation actions that prevented the extinction of GLTs three decades ago. We identify specific road sections along the highway and accompanying paved roads in the region that if equipped with tailored over passages would greatly reduce the road barrier effects. We also highlight areas where reforestation efforts could be extended in order to help reestablishing the connectivity between GLT habitat areas. We suggest that the working group integrating key decision makers and stakeholders, including the Non‐governmental organization leading the conservation efforts, partner universities, national road and environmental agencies, and the road construction company, to implement and to monitor the complementary road passages to improve connectivity of GLT habitat, and consequently to ensure the species' survival.
Sonographic assessment of nerve blood flow in diabetic neuropathy
Authors: Borire A. A. , Issar T. , Kwai N. C. , Visser L. H. , Simon N. G. , Poynten A. M. , Kiernan M. C. , Krishnan A. V.
Published: July 2019

Aims

To undertake sonographic assessment of nerve blood flow in people with Type 2 diabetes and correlate the findings with neuropathy severity scores and electrophysiological measurements.

Methods

Median and tibial nerve ultrasound scans were undertaken in 75 people with diabetes and 30 aged‐matched controls without diabetes, using a high‐resolution linear probe at non‐entrapment sites. Nerve blood flow was quantified using power Doppler techniques to obtain the vessel score and the maximum perfusion intensity. Neuropathy severity was assessed using a total neuropathy score.

Results

Diabetic nerves had higher rates of nerve blood flow detection (28%) compared to the control group (P < 0.0001). Significant correlations were found between nerve blood flow measurements and nerve size (P <0.001), reported sensory symptoms (P < 0.05) and neuropathy severity scores (P < 0.001). The cohort with diabetes had significantly larger median (8.5 ± 0.3 mm2 vs 7.2 ± 0.1 mm2; P < 0.05) and tibial nerves (18.0 ± 0.9 mm2 vs 12.8 ± 0.5 mm2; P < 0.05) compared with controls.

Conclusion

Peripheral nerve hypervascularity is detectable by ultrasonography in moderate to severe diabetic neuropathy with prominent sensory dysfunction.
The enduring effects of early‐life stress on the microbiota–gut–brain axis are buffered by dietary supplementation with milk fat globule membrane and a prebiotic blend
Authors: O'Mahony Siobhain M. , McVey Neufeld Karen‐Anne , Waworuntu Rosaline V. , Pusceddu Matteo M. , Manurung Sarmauli , Murphy Kiera , Strain Conall , Laguna Mamen C. , Peterson Veronica L. , Stanton Catherine , Berg Brian M. , Dinan Timothy G. , Cryan John F.
Published: July 2019

Nutritional interventions targeting the microbiota–gut–brain axis are proposed to modulate stress‐induced dysfunction of physiological processes and brain development. Maternal separation (MS) in rats induces long‐term alterations to behaviour, pain responses, gut microbiome and brain neurochemistry. In this study, the effects of dietary interventions (milk fat globule membrane [MFGM] and a polydextrose/galacto‐oligosaccharide prebiotic blend) were evaluated. Diets were provided from postnatal day 21 to both non‐separated and MS offspring. Spatial memory, visceral sensitivity and stress reactivity were assessed in adulthood. Gene transcripts associated with cognition and stress and the caecal microbiota composition were analysed. MS‐induced visceral hypersensitivity was ameliorated by MFGM and to greater extent with the combination of MFGM and prebiotic blend. Furthermore, spatial learning and memory were improved by prebiotics and MFGM alone and with the combination. The prebiotic blend and the combination of the prebiotics and MFGM appeared to facilitate return to baseline with regard to HPA axis response to the restraint stress, which can be beneficial in times where coping mechanisms to stressful events are required. Interestingly, the combination of MFGM and prebiotic reduced the long‐term impact of MS on a marker of myelination in the prefrontal cortex. MS affected the microbiota at family level only, while MFGM, the prebiotic blend and the combination influenced abundance at family and genus level as well as influencing beta‐diversity levels. In conclusion, intervention with MFGM and prebiotic blend significantly impacted the composition of the microbiota as well as ameliorating some of the long‐term effects of early‐life stress.
Emerging market capital flows and U.S. monetary policy
Authors: Clark John , Converse Nathan , Coulibaly Brahima , Kamin Steven B.
Published: July 2019

This paper analyzes the drivers of net private capital flows to emerging market economies (EMEs), focusing in particular on the policies of the Federal Reserve. We argue that the role of the Federal Reserve in EME capital flows has been smaller than popularly believed. We first show that the run‐up in capital flows to EMEs predated the loosening of Fed policy, while flows slowed substantially between 2010 and 2015, even as the Fed's quantitative easing program continued to add to monetary stimulus. Both the initial surge in capital flows to EMEs and their subsequent decline are better explained by swings in commodity prices and EME output growth, a linkage which we confirm through panel data regressions on capital flows to 20 major EMEs. The anticipation of the normalization of Federal Reserve policy appears not to have played a predominant role in the decline of capital flows to EME between 2010 and 2015.
Effects of unconventional monetary policy across U.S. industries
Authors: Berisha Edmond
Published: July 2019

Using industry‐level data for all U.S. states obtained from the U.S. Bureau of Economic Analysis, this paper examines the impact that unconventional monetary policy has had on six U.S. industries. The results indicate that the impact varies across the industries analysed. The results show that total wages and salaries increased the most in the finance sector. However, the strongest impact on total real output was in the wholesale sector.
Undergraduate nursing students’ stigma and recovery attitudes during mental health clinical placement: A pre/post‐test survey study
Authors: Foster Kim , Withers Elaine , Blanco Tony , Lupson Christine , Steele Michael , Giandinoto Jo‐Ann , Furness Trentham
Published: July 2019

Undergraduate nursing students have been reported to hold negative and stigmatizing attitudes towards mental health consumers and to be under‐prepared for mental health clinical placement. This study aimed to investigate undergraduate nurses’ stigma and recovery attitudes to mental illness, and describe their understandings of personal recovery on entry and exit to traditional mental health clinical placement. A pre/post‐test survey was administered to N = 249 nursing students in Australia. Demographic data, attitudes towards mental health nursing and clinical placement, the Opening Minds Scale for Healthcare Providers (OMS‐HC), Recovery Attitudes Questionnaire (RAQ‐7), and an open‐ended question on understandings of personal recovery from mental illness were collected on entry (T1) and exit (T2) to placement. At T1, students reported moderate stigma and positive attitudes towards recovery (OMS‐HC mean = 34.6; RAQ‐7 mean = 4.0). At T2, there was a reduction in stigma (social distance P = 0.02, d = 0.26) and improvement in recovery attitudes (P < 0.01, d = 0.40). Attitudes towards mental health nursing and placement also improved (P < 0.01). Having a family member with mental illness predicted improvements in stigma and recovery attitudes. On entry to placement, most students described accurate understandings of personal recovery, which were maintained during placement. The findings indicate that mental health clinical placements are effective in improving students’ mental health stigma and recovery attitudes and provide a prime opportunity to attract students into the field. Co‐produced or consumer‐led education provided by peer workers during clinical placements may improve students’ stigmatizing attitudes and stimulate their interest to work in the field.
Estimation of influenza‐ and respiratory syncytial virus‐attributable medically attended acute respiratory infections in Germany, 2010/11‐2017/18
Authors: an der Heiden Matthias , Buchholz Udo , Buda Silke
Published: July 2019

Background

The burden of influenza in primary care is difficult to assess, since most patients with symptoms of a respiratory infection are not tested. The case definition of “medically attended acute respiratory infection” (MAARI) in the German physician sentinel is sensitive; however, it requires modelling techniques to derive estimates of disease attributable to influenza and respiratory syncytial virus (RSV).

Objectives

The objective of this paper was to review and extend our previously published model in order to estimate the burden of RSV and the differential burden of the two influenza B lineages (Victoria, Yamagata) as well as both influenza A subtypes on primary care visits.

Methods

Data on MAARI and virological results of respiratory samples (virological sentinel) were available from 2010/11 until 2017/18. We updated the previously published generalized additive regression model to include RSV.

Results

We found that the proportion of MAARI due to RSV is substantial only in the 0‐1‐ and 2‐4‐year‐old age groups (0‐1 years old: median 7.5%, range 4.0%‐14.8%; 2‐4 years old: median 6.5%, range 4.0%‐10.3%); in the 0‐1 years old age group, RSV leads in almost all seasons to a higher burden than any influenza type or subtype, but this is reversed in the age group 2‐4 years old.

Conclusions

We succeeded in rearranging our previously published model on MAARI to incorporate RSV as well as the two influenza B lineages (Victoria, Yamagata) in the time period 2010 to 2018.
Through the “Eyes” of the Machine
Authors: Tarran Brian
Published: July 2019

The AI: More Than Human exhibition at the Barbican, London, gave a glimpse of the world as it is seen by our artificial intelligence tools. Brian Tarran reports
The S Word … and What to do about it
Authors: Tarran Brian
Published: July 2019

What do we do about significance?
Complacency at the Gates
Authors: Cready William M.
Published: July 2019

A field report on the non-impact of the ASA Statement on Statistical Significance and P-Values on the broader research community. By William M. Cready
The Deadly Facets of Terrorism
Authors: Python Andre , Illian Janine B. , Jones-Todd Charlotte M. , Blangiardo Marta
Published: July 2019

Can Bayesian models reveal the underlying processes that drive the lethality of non-state terrorism at a local level? Andre Python, Janine B. Illian, Charlotte M. Jones-Todd and Marta Blangiardo investigate
Military Vital Statistics the Spanish Flu and the First World War
Authors: Molgaard Craig A.
Published: July 2019

Craig A. Molgaard explores the origins, spread and impact of the deadly influenza pandemic of 1918–1919, and how the outbreak intersected with the end of the First World War
The structure and electrical properties of Ca0.6(Li0.5Bi0.5‐xPrx)0.4Bi2Nb2O9 high‐temperature piezoelectric ceramics
Authors: Wang Dan , Xu Yugen , Shi Yulin , Wang Hongliang , Wu Xiaojun , Wu Chao , Zhu Jianguo , Chen Qiang
Published: July 2019

Ca0.6(Li0.5Bi0.5‐xPrx)0.4Bi2Nb2O9 ceramics were prepared via a solid‐state reaction method. The effect of the Pr content on the structural and electrical properties was systematically investigated. X‐ray diffraction (XRD) combined with Rietveld refinement and X‐ray photoelectron spectroscopy (XPS) demonstrated that a moderate amount of Pr3+ can be incorporated into the NbO6 octahedra, while excess Pr3+ ions probably enter into the (Bi2O2)2+ layers, thus resulting in an increase in the tetragonality of the crystal structure. The introduction of Pr suppressed the generation of oxygen vacancies and improved the preferential grain growth along the c‐axis, which might be responsible for enhancing the resistivity (ρ ~ 106 Ω cm at 600°C). The replacement of Pr3+ for A‐site Bi3+ enhanced the piezoelectric property, and the piezoelectric constant d33 increased from 13.8 pC/N to 16.3 pC/N. The high depolarization temperature (up to 900°C) implied that CBN‐LBP100x ceramics are promising candidates for ultrahigh‐temperature application.
The Right to Privacy, Control Over Self‐Presentation, and Subsequent Harm
Authors: Munch Lauritz Aastrup
Published: July 2019

Abstract

Andrei Marmor has recently offered a narrow interpretation of the right to privacy as a right to having a reasonable amount of control over one's self‐presentation. He claims that the interest people have in preventing others from abusing their personal information to do harm is not directly protected by the right to privacy. This article rejects that claim and defends a view according to which concerns about abuse play a central role in fleshing out the appropriate scope of a general right to privacy.
Leadless pacing with Micra TPS: A comparison between right ventricular outflow tract, mid‐septal, and apical implant sites
Authors: Garweg Christophe , Vandenberk Bert , Foulon Stefaan , Haemers Peter , Ector Joris , Willems Rik
Published: July 2019

Background

With its steerable transcatheter delivery system, the Micra can be deployed in nonapical positions within the right ventricle, potentially allowing reduction of the paced QRS width. We sought to evaluate the safety and long‐term performance of the right ventricular outflow tract (RVOT) pacing using the Micra transcatheter pacing system (TPS). We also compared the paced QRS between RVOT, mid‐septal, and apical implant positions.

Methods

All patients who underwent a Micra TPS implantation at the University Hospitals of Leuven were enrolled in this observational study. Right ventricular (RV) position of the device was assessed on per‐procedural ventriculography. Paced QRS was analyzed and follow‐up completed at 1 month and then every 6 months.

Results

Among the 133 patients included (mean follow‐up: 13 ± 11 months), 45 were implanted in the RVOT, 58 midseptally, and 30 at the apex. All implant procedures were successful and no pericardial effusion was encountered within the 30 days post‐implant. Two major complications were reported with devices implanted at the apex. Pacing impedance was significantly higher in the RVOT compared to the mid‐septal and apical position (P < .001). Pacing threshold and R‐wave amplitude did not differ over time in either position. The median narrowest paced QRS duration was observed in the RVOT (142 ms) compared to mid‐septal (159 ms; P < .001), and apical position (181 ms; P < .001).

Conclusion

Implantation of the Micra TPS in the RVOT is safe and feasible. Electrical performance over time was comparable to mid‐septal and apical positions. The narrowest paced QRS complexes is achieved with RVOT pacing.
Antiarrhythmic Drugs in Atrial Fibrillation: Is There Still a Role for Rhythm Control?
Authors: Rich Michael W.
Published: July 2019

This editorial comments on the article by Dalgaard et al.
Can smart factories bring environmental benefits to their products?: A case study of household refrigerators
Authors: Zhang Wujie , Gu Fu , Guo Jianfeng
Published: July 2019

Smart factories have been widely adopted as a new manufacturing paradigm, in which the state‐of‐the‐art technologies are introduced to improve relevant processes. Yet, whether smart factories affect the environmental performance remains unknown. In this article, we examine the environmental performance of a smart refrigerator factory by comparing the environmental impacts of its product to a similar model that is produced in a traditional fashion. This article quantifies and verifies the theoretically predicted impacts of this smart factory on the individual processes. Though the overall differences in the two models are quite minor, we find that this smart factory can notably reduce the values of most impact categories associated with the parts and refrigerator production; the reduction in the value of climate change is 33%. Owing to higher material efficiency—raw material savings in this smart factory contributes to the greatest reductions in most categorized impacts—the contribution to the reduction of climate change is 39%. Yet, all categorized impacts of procurement and delivery are increased due to product personalization and direct delivery. The results of sensitivity analysis show that promoting product modularity, adopting clean energy such as wind power can further improve the environmental performance of the selected refrigerator. The introduction of auxiliary equipment and systems slightly increases the value of each category; yet their impacts are negligible compared to their benefits as facilitating production efficiency. Based on the quantitative results, recommendations are given to improve the environmental performance of smart factory, including optimizing current strategies and promoting horizontal and end‐to‐end integration.
Complications and reproductive outcome after uterine artery embolization for retained products of conception
Authors: Ohmaru‐Nakanishi Takako , Kuramoto Kazutaka , Maehara Miyako , Takeuchi Reiko , Oishi Hiroko , Ueoka Yosuke
Published: July 2019

Aim

The purpose of this study was to evaluate the complications and reproductive outcome after uterine artery embolization (UAE) for retained products of conception (RPOC).

Methods

This was a retrospective medical‐records review study of 57 women treated for RPOC. Participants were divided into two groups: women who underwent treatment with UAE (UAE group: n = 32, 56.1%) and those without UAE (control group: n = 25, 43.9%). The complications and reproductive outcomes were compared between the two groups. Information on subsequent pregnancies and their outcomes was available for 30 women who attempted to conceive.

Results

There were no significant differences in the interval from the last delivery or abortion (40.1 ± 3.4 vs 51.0 ± 5.1 months, respectively; P = 0.16), the rate of severe bleeding under hysteroscopy (18.5 vs 9.1%, respectively; P = 0.65), the conception rate (58.8 vs 61.5%, respectively; P = 1.0) and mean time to conception (9.9 ± 1.6 vs 11.0 ± 2.9 months, respectively; P = 0.17) in women in the UAE group compared with those in the control group. Rates of post‐partum hemorrhage (PPH) and manual removal of placenta (25.0% in the UAE group and 16.7% in the control group, respectively) were higher than the general population.

Conclusion

Selective UAE for RPOC may be a preferable procedure in women who are suspected as having a risk of severe bleeding under treatment. Women who were treated for RPOC, regardless of UAE, were at risk of PPH and difficulty in removing the placenta in future pregnancies.
Identification, occurrence, incidence and transmission of phytoplasma associated with Petunia violacea witches’ broom in Iran
Authors: Hemmati Chamran , Nikooei Mehrnoosh , Bertaccini Assunta
Published: July 2019

A petunia witches’ broom (PvWB) disease, characterized by phyllody, virescence, witches’ broom, little leaf and yellowing, was observed in municipal lands and parks in Bandar Abbas, Hormozgan province, Iran. The disease was present with an average incidence of 20%. PCR and sequencing analysis carried out on selected samples from symptomatic plants showed the presence of a phytoplasma associated with the disease. The molecular comparison of the 16S ribosomal gene indicated 99% sequence identity with the one of “Candidatus Phytoplasma australasia”. This phytoplasma was transmitted to healthy petunia plants under experimental conditions by the leafhopper Orosius albicinctus that was then demonstrated to be a vector of this phytoplasma.
Monarch butterflies use an environmentally sensitive, internal timer to control overwintering dynamics
Authors: Green Delbert A. , Kronforst Marcus R.
Published: July 2019

The monarch butterfly (Danaus plexippus) complements its iconic migration with diapause, a hormonally controlled developmental programme that contributes to winter survival at overwintering sites. Although timing is a critical adaptive feature of diapause, how environmental cues are integrated with genetically‐determined physiological mechanisms to time diapause development, particularly termination, is not well understood. In a design that subjected western North American monarchs to different environmental chamber conditions over time, we modularized constituent components of an environmentally‐controlled, internal diapause termination timer. Using comparative transcriptomics, we identified molecular controllers of these specific diapause termination components. Calcium signalling mediated environmental sensitivity of the diapause timer, and we speculate that it is a key integrator of environmental condition (cold temperature) with downstream hormonal control of diapause. Juvenile hormone (JH) signalling changed spontaneously in diapause‐inducing conditions, capacitating response to future environmental condition. Although JH is a major target of the internal timer, it is not itself the timer. Epigenetic mechanisms are implicated to be the proximate timing mechanism. Ecdysteroid, JH, and insulin/insulin‐like peptide signalling are major targets of the diapause programme used to control response to permissive environmental conditions. Understanding the environmental and physiological mechanisms of diapause termination sheds light on fundamental properties of biological timing, and also helps inform expectations for how monarch populations may respond to future climate change.
Alternative splicing event modifying ADGRL1/latrophilin‐1 cytoplasmic tail promotes both opposing and dual cAMP signaling pathways
Authors: Ovando‐Zambrano José‐Carlos , Arias‐Montaño José‐Antonio , Boucard Antony A.
Published: July 2019

The adhesion G protein–coupled receptor ADGRL1/latrophilin‐1 (LPHN1) stabilizes synapse formation through heterophilic interactions. A growing consensus is pointing to the role of LPHN1 in modulating intracellular levels of cAMP, although conflicting data exist. Variants of LPHN1 resulting from alternative splicing differ at multiple sites, two of which, designated as SSA and SSB, modify extracellular and intracellular receptor regions, respectively. While SSA splicing modulates receptor–ligand affinity, the function of SSB splicing remains elusive. Here, we explored the role of SSB in an attempt to unify current findings on LPHN1 signaling pathways by testing SSB‐containing and SSB‐deficient receptor variants in signaling paradigms involving interaction with their ligands neurexin and FLRT. cAMP competitive binding assays revealed that cells expressing either receptor variant exhibited a ligand‐dependent decrease in the forskolin‐induced cAMP accumulation. Surprisingly, the expression of SSB‐containing LPHN1 promoted both constitutive and ligand‐dependent cAMP production, whereas SSB‐deficient LPHN1 did not. Pertussis toxin treatment unveiled a constitutive coupling to Gαi/o for SSB‐containing LPHN1 while abrogating the ligand‐mediated activation of Gαs. Importantly, neither receptor variant increased the intracellular concentration of Ca2+ nor MAP kinase activation in the presence of ligands. These results suggest that SSB splicing selectively affects the duality of LPHN1 signaling toward opposing cAMP pathways.
Institutional Analysis with the Institutional Grammar
Authors: Siddiki Saba , Heikkila Tanya , Weible Christopher M. , Pacheco‐Vega Raul , Carter David , Curley Cali , Deslatte Aaron , Bennett Abby
Published: July 2019

Institutions are strategies, norms, and rules embodied in public policies and/or social conventions. They reflect and establish expectations about who can do what, where, and how, and are often employed for resolving collective action dilemmas and other kinds of governance challenges. Given their salience, social science scholars have dedicated substantial effort to developing analytical approaches for understanding the design, function, and performance of institutions. Particularly valuable are approaches that generalize across institutional types and are versatile enough to be paired with multiple concepts, theories, and methods. This paper focuses on one such approach, called the Institutional Grammar. The Institutional Grammar is an approach for assessing the structure and content of institutions. It received limited attention immediately following its introduction. In recent years, however, numerous journal articles have been published that highlight the promise of the Institutional Grammar for supporting rigorous analyses of institutional design and associated outcomes within the context of various theoretical, conceptual, and methodological approaches. This article (i) reintroduces parts of the Institutional Grammar; (ii) summarizes the theoretical, methodological, and empirical foci of all journal articles published to date that address it; and (iii) presents an agenda for advancing the study of institutions using the Institutional Grammar.
Editors’ Introduction: Aligning Implicit Learning and Statistical Learning: Two Approaches, One Phenomenon
Authors: Rebuschat Patrick , Monaghan Padraic
Published: July 2019

This editors’ introduction provides the background to the special issue. We first outline the rationale for bringing together, in a single volume, leading researchers from two distinct, yet related research strands, implicit learning and statistical learning. The aim of the special issue is to facilitate the development of a shared understanding of research questions and methodologies, to provide a platform for discussing similarities and differences between the two strands, and to encourage the formulation of joint research agendas. We then introduce the new contributions solicited for this special issue and provide our perspective on the agenda setting that results from combining these two approaches.
Canine histiocytic sarcoma cell lines with SHP2 p.Glu76Gln or p.Glu76Ala mutations are sensitive to allosteric SHP2 inhibitor SHP099
Authors: Tani Hiroyuki , Kurita Sena , Miyamoto Ryo , Ochiai Kazuhiko , Tamura Kyoichi , Bonkobara Makoto
Published: July 2019

Some canine cases of histiocytic sarcoma (HS) carry an activating mutation in the src homology two domain‐containing phosphatase 2 (SHP2) encoded by PTPN11. SHP099 is an allosteric inhibitor of SHP2 that stabilizes SHP2 in a folded, auto‐inhibited conformation. Here, we examined the expression and mutation status of SHP2 in five canine HS cell lines and evaluated the growth inhibitory properties of SHP099 against these cell lines. All five of the canine HS cell lines expressed SHP2, with three of the lines each harbouring a distinct mutation in PTPN11/SHP2 (p.Glu76Gln, p.Glu76Ala and p.Gly503Val). In silico analysis suggested that p.Glu76Gln and p.Glu76Ala, but not p.Gly503Val, promote shifting of the SHP2 conformation from folded to open‐active state. SHP099 potently suppressed the growth of two of the mutant cell lines (harbouring SHP2 p.Glu76Gln or p.Glu76Ala) but not that of the other three cell lines. In addition, SHP099 suppressed ERK activation in the cell line harbouring the SHP2 p.Glu76Ala mutation. The SHP2 p.Glu76Gln and p.Glu76Ala mutations are considered to be activating mutations, and the signal from SHP2 p.Glu76Ala is inferred to be transduced primarily via the ERK pathway. Moreover, SHP099‐sensitive HS cells, including those with SHP2 p.Glu76Gln or p.Glu76Ala mutations, may depend on these mutations for growth. Therefore, targeting cells harbouring SHP2 p.Glu76Gln and p.Glu76Ala with SHP099 may be an approach for the treatment of canine HS.
Acremonium and trichosporon fungal keratoconjunctivitis in a Leopard Gecko (Eublepharis macularius)
Authors: Munevar Christian , Moore Bret A. , Gleeson Molly D. , Ozawa Sarah M. , Murphy Christopher J. , Paul‐Murphy Joanne R. , Leonard Brian C.
Published: July 2019

A 6‐year‐old male leopard gecko (Eublepharis macularius) was presented with a 2‐year history of recurrent dysecdysis involving the ocular surface of both eyes. Ophthalmic examination revealed ocular surface desiccation and multifocal superficial ulcerative keratitis with patchy remnants of retained shed. Other abnormalities included stomatitis and mandibular and maxillary osteomyelitis. Topical and systemic antibiotic therapy, oral vitamin A, and improved husbandry conditions resolved the stomatitis and osteomyelitis but did not improve the ocular surface. Corneal cytology collected with a cytobrush revealed branching hyphae and budding yeast consistent with fungal keratitis. Fungal culture grew Acremonium sp. and Trichosporon sp. The addition of topical antifungal therapy improved the ocular surface health, but the patient was euthanized 7 weeks after initial presentation for persistent vomiting and dyspnea. Necropsy was declined. This case describes the first case of fungal keratitis caused by Acremonium sp. and Trichosporon sp. in a reptile.
Probing the Force Field to Identify Potential Energy
Authors: Xu Yawen , Virgin Lawrence N.
Published: July 2019

A small ball resting on a curve in a gravitational field offers a simple and compelling example of potential energy. The force required to move the ball, or to maintain it in a given position on a slope, is the negative of the vector gradient of the potential field: the steeper the curve, the greater the force required to push the ball up the hill (or keep it from rolling down). We thus observe the turning points (horizontal tangency) of the potential energy shape as positions of equilibrium (in which case the “restoring force” drops to zero). In this paper, we appeal directly to this type of system using both one- and two-dimensional shapes: curves and surfaces. The shapes are produced to a desired mathematical form generally using additive manufacturing, and we use a combination of load cells to measure the forces acting on a small steel ball-bearing subject to gravity. The measured forces, as a function of location, are then subject to integration to recover the potential energy function. The utility of this approach, in addition to pedagogical clarity, concerns extension and applications to more complex systems in which the potential energy would not be typically known a priori, for example, in nonlinear structural mechanics in which the potential energy changes under the influence of a control parameter, but there is the possibility of force probing the configuration space. A brief example of applying this approach to a simple elastic structure is presented.
Simultaneous Shape and Topology Optimization of Planar Linkage Mechanisms Based on the Spring-Connected Rigid Block Model
Authors: Yu Jeonghan , Han Sang Min , Kim Yoon Young
Published: July 2019

Using the topology optimization can be an effective means of synthesizing planar rigid-body linkage mechanisms to generate desired motion, as it does not require a baseline mechanism for a specific topology. While most earlier studies were mainly concerned with the formulation and implementation of topology optimization-based synthesis in a fixed grid, this study aims to realize the simultaneous shape and topology optimization of planar linkage mechanisms using a low-resolution spring-connected rigid block model. Here, we demonstrate the effectiveness of simultaneous optimization over a higher-resolution fixed-grid rigid block-based topology optimization process. When shape optimization to change the block shapes is combined with topology optimization to synthesize the mechanism, the use of low-resolution discretized models improves the computation efficiency considerably and helps to yield compact mechanisms with less complexity, making them more amenable to fabrication. After verifying the effectiveness of the simultaneous shape and topology optimization process with several benchmark problems, we apply the method to synthesize a mechanism which guides a planar version of a human's gait trajectory.
Sound-source localization as a multisystem process: The Wallach azimuth illusion
Authors: Yost William A. , Pastore M. Torben , Pulling Kathryn R.
Published: July 2019

Wallach [J. Exp. Psychol. 27, 339–368 (1940)] described a “2-1” rotation scenario in which a sound source rotates on an azimuth circle around a rotating listener at twice the listener's rate of rotation. In this scenario, listeners often perceive an illusionary stationary sound source, even though the actual sound source is rotating. This Wallach Azimuth Illusion (WAI) was studied to explore Wallach's description of sound-source localization as a required interaction of binaural and head-position cues (i.e., sound-source localization is a multisystem process). The WAI requires front-back reversed sound-source localization. To extend and consolidate the current understanding of the WAI, listeners and sound sources were rotated over large distances and long time periods, which had not been done before. The data demonstrate a strong correlation between measures of the predicted WAI locations and front-back reversals (FBRs). When sounds are unlikely to elicit FBRs, sound sources are perceived veridically as rotating, but the results are listener dependent. Listeners' eyes were always open and there was little evidence under these conditions that changes in vestibular function affected the occurrence of the WAI. The results show that the WAI is a robust phenomenon that should be useful for further exploration of sound-source localization as a multisystem process.
Social amoebae establish a protective interface with their bacterial associates by lectin agglutination
Authors: Farinholt Timothy , Dinh Christopher , Kuspa Adam
Published: July 2019

Dictyostelium
social amoebae agglutinate bacteria with a secreted lectin to optimize their survival during feeding.
AAV-delivered eCD4-Ig protects rhesus macaques from high-dose SIVmac239 challenges
Authors: Gardner Matthew R. , Fellinger Christoph H. , Kattenhorn Lisa M. , Davis-Gardner Meredith E. , Weber Jesse A. , Alfant Barnett , Zhou Amber S. , Prasad Neha R. , Kondur Hema R. , Newton Wendy A. , Weisgrau Kimberly L. , Rakasz Eva G. , Lifson Jeffrey D. , Gao Guangping , Schultz-Darken Nancy , Farzan Michael
Published: July 2019

AAV-expressed eCD4-Ig protects rhesus macaques from SIVmac239.
Multifunctional scaffolds for facile implantation, spontaneous fixation, and accelerated long bone regeneration in rodents
Authors: Zhang Ben , Skelly Jordan D. , Maalouf Jacob R. , Ayers David C. , Song Jie
Published: July 2019

Self-stiffening, macroporous, shape-memory scaffolds delivering a low dose of osteogenic factors accelerate segmental long bone regeneration in rats.
More blurred lines with innate lymphoid cells
Authors: Brunner Patrick M.
Published: July 2019

Group 2 innate lymphoid cells might form a pool of innate cells with capabilities beyond fighting parasites and mediating allergic diseases.
Polyamine Depletion Abrogates Enterovirus Cellular Attachment
Authors: Kicmal Thomas M. , Tate Patrick M. , Dial Courtney N. , Esin Jeremy J. , Mounce Bryan C.
Published: July 2019

Enteroviruses are significant human pathogens that can cause severe disease. These viruses rely on polyamines, small positively charged molecules, for robust replication, and polyamine depletion limits infection
in vitro
and
in vivo
. The mechanisms by which polyamines enhance enteroviral replication are unknown. Here, we describe how Coxsackievirus B3 (CVB3) utilizes polyamines to attach to susceptible cells and initiate infection. Using a forward genetic screen, we identified a mutation in a receptor-binding amino acid that promotes infection of polyamine-depleted cells. These data suggest that pharmacologically inhibiting polyamine biosynthesis may combat virus infection by preventing virus attachment to susceptible cells.
Draft Genome Sequence of Filamentous Fungus
Phialemoniopsis curvata
, Isolated from Diesel Fuel
Authors: Varaljay Vanessa A. , Lyon Wanda J. , Crouch Audra L. , Drake Carrie A. , Hollomon Jeffrey M. , Nadeau Lloyd J. , Nunn Heather S. , Stevenson Bradley S. , Bojanowski Caitlin L. , Crookes-Goodson Wendy J.
Published: July 2019

Phialemoniopsis curvata
D216 is a filamentous fungus isolated from contaminated diesel fuel. The genome size is 40.3 Mbp with a G+C content of 54.81%. Its genome encodes enzymes and pathways likely involved in the degradation of and survival in fuel, including lipases, fatty acid transporters, and beta oxidation.
Complete Genome Sequence of Brevibacillus laterosporus Bl-zj, an Algicidal Bacterium Isolated from Soil
Authors: Cai Jian , Chen Dianyu , Chen Dong , Huang Xianghu , Li Changling , Liu Huiling , Li Mengjie , Li Guanbao , Zhang Yulei
Published: July 2019

Brevibacillus laterosporus
can be used as a biocontrol agent for varieties of plants, as it is a pathogen of invertebrates and can also inhibit many bacteria and fungi. Here, we describe the complete genome sequence of
B. laterosporus
strain Bl-zj, an algicidal bacterium on cyanobacteria isolated from the soil in China.
Draft Genome Sequences of Antimicrobial-Resistant
Shigella
Clinical Isolates from Pakistan
Authors: Lomonaco Sara , Lascols Christine , Crawford Matthew A. , Anderson Kevin , Hodge David R. , Fisher Debra J. , Pillai Segaran P. , Morse Stephen A. , Khan Erum , Hughes Molly A. , Allard Marc W. , Sharma Shashi K.
Published: July 2019

Shigella
spp. are the most common cause of dysentery in developing countries and the second leading cause of diarrheal deaths worldwide. Multidrug-resistant (MDR)
Shigella
spp. are a serious threat to global health. Herein, we report draft genome sequences for three MDR
Shigella
isolates from Pakistan, two
Shigella flexneri
isolates and one
Shigella sonnei
isolate.
Transcriptomic Analysis of
Mucor irregularis
Containing a Negative Single-Stranded RNA Mycovirus
Authors: Barata Rafael R. , Vianez-Júnior João L. S. G. , Nunes Márcio R. T.
Published: July 2019

The fungus
Mucor irregularis
is a causative agent of mucormycosis. The transcriptome analysis of the isolated
M. irregularis
strain C3B revealed the presence of an RNA polymerase domain of a negative-polarity RNA virus. In this work, we describe the gene ontology-based annotation of the
Mucor irregularis
transcriptome, which includes a putative RNA mycovirus.
Complete Genome Sequence of Enterotoxigenic Escherichia coli Myophage LL12
Authors: Piya Denish , Lessor Lauren , Liu Mei , Gill Jason J.
Published: July 2019

This work describes the complete genome sequence of the virulent myophage LL12. The 136-kb LL12 genome is related to coliphage V5 and is a component in the prebiotic PreforPro. LL12 was isolated against enterotoxigenicEscherichia coli, which causes traveler’s diarrhea.
Complete Genome Sequence of Salmonella enterica Serovar Heidelberg Siphophage Sepoy
Authors: Marrufo Armando M. , Zeng Chi , O’Leary Chandler , Lessor Lauren , Kongari Rohit , Gill Jason , Liu Mei
Published: July 2019

Phage Sepoy infectsSalmonella entericaserovar Heidelberg, a Gram-negative bacterium that causes severe foodborne illnesses. Bacteriophages infecting this pathogen may be used as biocontrol agents for preventingSalmonellafoodborne diseases. Here, we present the complete genome sequence of Sepoy, a T5-like siphophage.
Rare cause of Bow Hunter’s syndrome due to an aberrant course of a vertebral artery
Authors: Tanaka Kaishin , Steinfort Brendan
Published: July 2019

Bow Hunter’s syndrome (BHS) is a rare cause of vertebrobasilar insufficiency and is reported to most commonly be caused by vertebral artery impingement on cervical vertebrae osteophytes. We report a case in a 56-year-old male patient who on investigation of recurrent posterior circulation ischaemic strokes was found to have BHS. The aetiology of the syndrome in this patient is due to a particularly unusual aberrancy in the path of the atlantoaxial portion of the culprit left vertebral artery. Aberrancy of the distal portion of the vertebral artery is in itself a rare entity, and there are few reports of it in relation to BHS. The patient in this case was successfully treated with endovascular sacrifice of the vertebral artery with no further dynamic occlusive symptoms.
Posterior urethral valve and anterior rectal duplication: a new combination
Authors: Bhandarkar Kailas P , Bouhadiba Nordeen , Garriboli Massimo
Published: July 2019

We present a rare case of association of anterior rectal duplication and posterior urethral valve (PUV). A term neonate with no antenatal concerns was admitted with urosepsis and acute renal injury at 18 days of age. History revealed a poor urinary stream and dribbling. After resuscitation and stabilisation, renal tract ultrasound and micturating cysto-urethrogram were performed. Cystourethroscopy showed PUV and a mass indenting the bladder posteriorly. MRI confirmed the presence of a cystic lesion anterior to the rectum suspicious of rectal duplication. Laparoscopic-assisted excision of the anterior rectal duplication cyst was then performed. The infant recovered uneventfully. Creatinine normalised postoperatively and has been stable at follow-up.
An acutely occluded Cabrol graft presenting as an acute coronary syndrome
Authors: Schulman-Marcus Joshua , Cochran-Caggiano Nicholas , El-Hajjar Mohammad , Singh Chanderdeep
Published: July 2019

The Cabrol technique employs a synthetic graft to connect the coronary arteries to an aortic graft in patients with complex disease of the ascending aorta. Acute Cabrol graft thrombosis is a life-threatening situation that presents as acute coronary syndrome, as it leads to acute coronary hypoperfusion. We present a patient with unstable anginal symptoms who had undergone aortic surgery 6 months prior to presentation. Cardiac catheterisation was concerning for aortic dissection yet was later revealed to be acute occlusion of a Cabrol graft. The patient ultimately died of cardiogenic shock. We review the Cabrol technique, complications and management of acute graft thrombosis.
Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis
Authors: Kanters Steve , Wilkinson Lars , Vrazic Hrvoje , Sharma Rohini , Lopes Sandra , Popoff Evan , Druyts Eric
Published: July 2019

Objective

To determine the comparative efficacy of once-weekly semaglutide relative to sodium-glucose cotransporter 2 inhibitors (SGLT-2is) licensed in Europe and North America among patients with type 2 diabetes (T2D) inadequately controlled with 1–2 oral antidiabetics (OADs), using a network meta-analysis (NMA). Design systematic review and network meta-analysis. Data Sources EMBASE, MEDLINE and CENTRAL were searched from January 1994 to August 2017.

Methods

Randomised controlled trials with ≥20 weeks of treatment evaluating once-weekly semaglutide or SGLT-2is. Primary outcomes included change from baseline in: HbA1c, weight, systolic blood pressure, postprandial blood glucose and fasting plasma glucose. Fixed-effect and random-effect Bayesian NMA were used to indirectly compare treatment effects at 26 (±4) weeks. Metaregression and sensitivity analyses were conducted. Model selection was performed using the deviance information criterion and consistency was assessed by comparing indirect (edge-splitting) to direct evidence.

Results

Forty-eight publications representing 21 trials were included. The mean differences (MD) in change from baseline in HbA1c of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from −0.56% for canagliflozin 300 mg (95% credible interval (CrI): −0.76 to −0.33%), to −0.95% for dapagliflozin 5 mg (95% CrI: −1.20 to −0.69%). The MD in change from baseline in weight of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from −1.35 kg for canagliflozin 300 mg to −2.48 kg for dapagliflozin 5 mg, while change from baseline in fasting plasma glucose ranged from −0.41 mmol/L for canagliflozin 300 mg to −1.37 mmol/L for dapagliflozin 5 mg. Once-weekly semaglutide was not statistically differentiable than all SGLT-2is in reducing systolic blood pressure. NMA was not feasible for postprandial blood glucose and safety outcomes.

Conclusion

Once-weekly semaglutide demonstrated statistically significant and clinically meaningful reductions in HbA1c and body weight in T2D patients inadequately controlled with 1–2 OADs compared to all SGLT-2is licensed in Europe and North America.