bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailoring of Painful Stimuli Used for Exploring Transfer of Function
Authors: Eilertsen Jon Magnus , Arntzen Erik
Published: March 2020

Fifteen college students rated the degree of painfulness of six images showing needle injections to different parts of a human hand. The images were rated on a scale ranging from 1 (not painful) to 5 (severely painful). Next, the participants were trained six conditional discriminations with abstract shapes as stimuli and tested for the formation of three 3-member equivalence classes in a one-to-many (OTM) training structure (AB/AC). The test for emergent relations were followed by training a novel set of stimuli (D) to the A stimuli. The needle injection images rated with the highest and lowest perceived degree of painfulness were used as stimulus D1 and D2, respectively. An image where the needle was replaced with a Q tip was used as stimulus D3 and assumed to be perceived as not painful. The DA training was followed by a matching-to-sample (MTS) test for the formation of three 4-member classes, and the participants were asked to choose one out of three identical bottles with water labelled with the B stimuli. Finally, the participants were asked to rate the degree of painfulness of the B stimuli. The main findings were that the B and D stimuli were not rated significantly different, indicating a transfer of function in the ratings from D to B stimuli. In addition, participants avoided choosing bottle B1 over B2 and B3, but they did not differentiate between B2 and B3.
Correction to: Non‑equivalence between all and canonical elaborations
Authors: Takahashi Satoru
Published: March 2020

The article Non‑equivalence between all and canonical elaborations, written by Satoru Takahashi.
Comparison and analyses of a variable span-morphing of the tapered wing with a varying sweep angle
Authors: Elelwi M. , Kuitche M.A. , Botez R.M. , Dao T.M.
Published: March 2020

This work presents a comparative study of design and development, in addition, of analyses of variable span morphing of the tapered wing (VSMTW) for the unmanned aerial vehicle (UAV). The proposed concept consists in the sliding of the inner section into the fixed part along the wing with varying the angle of the inner section inside the fixed part (parallel with the leading edge and the moving-wing axis is coincident to the fixed-wing axis) within two configurations. The wing design is based on a NACA 4412 aerofoil with the root chord of 0.675m and the tip chord of 0.367m for the fixed segment and 0.320m for the moving segment. Morphing wing analysis occurs at three selected locations that have been specified for extending and modifying span length by (25%, 50%, and 75%) of its original length to fulfill various flight mission requirements. The main objective of this paper is to compare the aerodynamic characteristics for several span lengths and sweep angles and to find their most efficient combinations. The wing is optimised for different velocities during all phases of flight (min speed, loiter, cruise, and max speed) which are 17, 34, 51, and 68m/s, respectively. The analyses are performed by computing forces (drag and lift) and moments at various altitudes, such as at the sea level, at 5,000 and 10,000ft. Two-dimensional aerodynamic analyses are carried out using XFLR5 code, and the ANSYS Fluent solver is used for investigating the flow field on the three-dimensional wing structure. It has been observed that a variable span morphing of tapered wing technology with a variable sweep angle can deliver up to 32.93% improved aerodynamic efficiency. This concept design can also be used for the aircraft roll motion technique instead of conventional control devices. Furthermore, the range flight mission increases up to 46.89% when the wing is placed at its full length compared to an original position. Finally, it has been concluded from this study that the wing design is more sensitive to the changing angle of the inner section and more efficient in terms of aerodynamic characteristics.
What Makes OIRA Work: A Commentary on Jim Tozzi’s “Office of Information and Regulatory Affairs: Past, Present, and Future”
Authors: Shelanski Howard
Published: March 2020

Jim Tozzi has for several decades been among the most dedicated and perceptive commentators on the White House Office of Information and Regulatory Affairs (OIRA). Indeed, Tozzi is arguably better suited than anyone to be the keeper of the OIRA flame: from his position in charge of the Office of Regulatory and Information Policy, OIRA’s predecessor organization, Tozzi contributed to the development of Executive Order (EO) 12291 and then stepped in as OIRA’s first Deputy Administrator. Since that time, he has been a steadfast defender of OIRA’s critical role in bringing rigorous analysis, quality control, and policy discipline to Executive Branch regulation. I share Tozzi’s view, and indeed that of all former OIRA officials I have spoken with, of OIRA’s importance to the regulatory state. Preservation of the strength and independence of the office is to me the principal criterion by which policy proposals that effect OIRA should be judged.
Cannabis Treatment in Children with Epilepsy: Practices of Canadian Neurologists
Authors: DeGasperis Stephanie M. , Webster Richard , Pohl Daniela
Published: March 2020

Background:

Medical cannabis has recently emerged as a treatment option for children with drug-resistant epilepsy. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about the attitudes of neurologists toward cannabinoid treatment of children with epilepsy.

Methods:

A 21-item online survey was distributed via email to 148 pediatric neurologists working in hospitals and community clinics across Canada. Questions were related to clinical practice and demographics.

Results:

This survey achieved a response rate of 38% (56 Canadian neurologists). These neurologists were treating 668 pediatric epilepsy patients with cannabinoids. While 29% of neurologists did not support cannabis treatment in their patients, 34% prescribed cannabis, and 38% referred to another authorizing physician, mostly to community-based non-neurologists. The majority of neurologists considered cannabis for patients with Dravet syndrome (68%) and Lennox–Gastaut syndrome (64%) after an average of three failed anticonvulsants. Twenty-seven percent considered it for patients with idiopathic generalized epilepsy, and 18% for focal epilepsy. No neurologist used cannabis as a first-line treatment. All neurologists had at least one hesitation regarding cannabis treatment in pediatric epilepsy. The most common one was poor evidence (66%), followed by poor quality control (52%) and high cost (50%).

Conclusions:

The majority of Canadian pediatric neurologists consider using cannabis as a treatment for epilepsy in children. With many gaps in evidence and high patient-driven demand for cannabis therapy, this survey provides immediate information from the “wisdom of the crowd,” to aid neurologists until further evidence is available.
Outcomes associated with scale-up of the Stepping On falls prevention program: A case study in redesigning for dissemination
Authors: Mahoney Jane E. , Gangnon Ron , Clemson Lindy , Jaros LaVerne , Cech Sandy , Renken Jill
Published: March 2020

Introduction:

Translating complex behavior change interventions into practice can be accompanied by a loss of fidelity and effectiveness. We present the evaluation of two sequential phases of implementation of a complex evidence-based community workshop to reduce falls, using the Replicating Effective Programs Framework. Between the two phases, workshop training and delivery were revised to improve fidelity with key elements.

Methods:

Stepping On program participants completed a questionnaire at baseline (phase 1: n = 361; phase 2: n = 2219) and 6 months post-workshop (phase 1: n = 232; phase 2: n = 1281). Phase 2 participants had an additional follow-up at 12 months (n = 883). Outcomes were the number of falls in the prior 6 months and the Falls Behavioral Scale (FaB) score.

Results:

Workshop participation in phase 1 was associated with a 6% reduction in falls (RR = 0.94, 95% CI 0.74–1.20) and a 0.14 improvement in FaB score (95% CI, 0.11– 0.18) at 6 months. Workshop participation in phase 2 was associated with a 38% reduction in falls (RR = 0.62, 95% CI 0.57–0.68) and a 0.16 improvement in FaB score (95% CI 0.14–0.18) at 6 months, and a 28% reduction in falls (RR = 0.72, 95% CI 0.65–0.80) and a 0.19 score improvement in FaB score (95% CI 0.17–0.21) at 12-month follow-up.

Conclusions:

Effectiveness can be maintained with widespread dissemination of a complex behavior change intervention if attention is paid to fidelity of key elements. An essential role for implementation science is to ensure effectiveness as programs transition from research to practice.
Using a television programme as a tool to increase perceived awareness of mental health and well-being – findings from ‘Our Mental Health’ survey
Authors: McTernan N. , Ryan F. , Williamson E. , Chambers D. , Arensman E.
Published: March 2020

Background:

International research shows that media can increase knowledge, raise public awareness and reduce stigma relating to mental health.

Methods:

Following the broadcast of a documentary on national television featuring interviews with young people who had experienced mental health difficulties and suicidal behaviour, an anonymous online survey, aimed at examining public perceptions of the impact of a television documentary, was conducted, using a mixed methods approach.

Results:

2311 people completed the survey. Of those who watched the documentary and answered the closed questions (n = 854), 94% stated that the documentary will positively impact young people’s mental health and well-being. The majority (91%) stated that the documentary will encourage young people to talk to someone if experiencing difficulties and 87% indicated it will help to reduce stigma associated with mental health. Viewers had a 5% higher level of intention to seek help than non-viewers. Participants indicated that the identifiable personal stories and discourse around stigma and shame, and the increased understanding and awareness gained, had the most profound impact on them.

Conclusions:

These findings indicate that a documentary addressing mental health and suicidal behaviour, which incorporates real life identifiable stories of resilience and recovery, has the potential to impact positively on emotional well-being and general mood, to reduce stigma related to mental health and to encourage help-seeking behaviour. Documentaries including these concepts, with a public mental health focus and a consistent message, incorporating pre- and post-evaluations, and customisation for target audiences in compliance with current media recommendations, should be considered.
The association between the maternal diet and the maternal and infant gut microbiome: a systematic review
Authors: Maher Siofra E. , O’Brien Eileen C. , Moore Rebecca L. , Byrne David F. , Geraghty Aisling A. , Saldova Radka , Murphy Eileen F. , Van Sinderen Douwe , Cotter Paul D. , McAuliffe Fionnuala M.
Published: March 2020

During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S ribosomal RNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/d) and fibre (g/d) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.
Huriella flakusii (Teloschistaceae, lichenized Ascomycota), a new species from the Colca Canyon region in Peru
Authors: Wilk Karina
Published: March 2020

A new species, Huriella flakusii, is described from the arid region of the Colca Canyon in southern Peru, and is characterized by squamulose, orange thalli and abundant, crowded and aggregated, usually flexuous when compressed, reddish apothecia. The thalline cortex, proper margin and hypothecium are paraplectenchymatous. The ascospores are broadly ellipsoid, 10‒15 × 5.0‒9.5 µm, with rather thin septa, 2‒4 µm. Phylogenetic analyses of the DNA sequences of ITS, nuLSU and mrSSU rDNA markers revealed that the new species is nested within the Amundsenia-Squamulea subclade in the subfamily Xanthorioideae, and has a sister group relationship to Huriella loekoesiana from South Korea.
The Political Representation of Economic Interests
Authors: Elkjær Mads Andreas , Iversen Torben
Published: March 2020

Rising inequality has caused concerns that democratic governments are no longer responding to majority demands, an argument the authors label thesubversion of democracy model(sdm). Thesdmcomes in two forms: one uses public opinion data to show that policies are strongly biased toward the preferences of the rich; the other uses macrolevel data to show that governments aren’t responding to rising inequality. This article critically reassesses thesdm, points to potential biases, and proposes solutions that suggest a different interpretation of the data, which the authors label therepresentative democracy model(rdm). After testing thesdmagainst therdmon public opinion data and on a new data set on fiscal policy, they find that middle-class power has remained remarkably strong over time, even as inequality has risen. The authors conclude that the rich have little influence on redistributive policies, and that the democratic state is apparently not increasingly constrained by global capital.
CONNECTING THE NORTHERN ANDES AND THE ATLANTIC. THE ROLE OF INLAND PORTS IN NEW GRANADA'S INTERREGIONAL TRADE (1770-1809)
Authors: Torres-Moreno James V. , Henao-Giraldo José L.
Published: March 2020

This paper analyses the role of Mompox in New Granada's interregional trade during the late colonial period. It focuses on the value, structure and destination of exports of domestic goods from Mompox to markets on the Atlantic and the Andes. By unearthing unexplored sources, this paper provides evidence that will help to understand, indirectly, some issues such as the nature and timing of economic growth, the degree of regional specialisation and, above all, the role of inland ports in the economic geography of the viceroyalty. The paper contends, first, that the region experienced a boom–bust cycle during the late colonial period. The export of domestic goods doubled between 1770 and 1800 but subsequently collapsed during the 1802-1809 years. Second, evidence suggests that the region experienced a process of market deepening and widening. Trade flows, then, played a larger role in shaping the economic history of the region than previously thought.
Exile Boundary Crossing: Aesthetic Objects and Perception in the Works of Walter Benjamin and María Zambrano
Authors: Enquist Källgren Karolina
Published: March 2020

In the late works of María Zambrano (1904–1991), the author presents exile as a particular kind of experience, by which the structure and arquitectonics of human existence become visible. Similarly, in his posthumously published Passagen-Werk Walter Benjamin (1892–1940) introduces the flanêur – which he repeatedly likens to the immigrant or exile – as the representation of a particular kind of gaze, disclosing the arquitectonics and structure of capitalist bourgeois society. In this article, I suggest that the notions of figura and dialektisches Bild from the authors’ respective works are connected to an exile mode of perception, centred on the problem of translatability across cultural and linguistic borders. I believe that the similarities between the two authors can be explained by a reading which contextualizes them as a political generation with a shared experience of exilic boundary-crossing.
Seminaries and Discipleship: Exploring Future Directions
Authors: Spencer Stephen
Published: March 2020

Theological colleges and seminaries across the Anglican Communion are at a crossroads and this essay proposes a reorientation of their life towards serving the intentional discipleship of the whole people of God. This kind of change would affect the culture as well as the content of what they do. For example, their pedagogy could become that of ‘the flipped classroom’, where ordinands engage in an apprenticeship style of learning, with their time in college falling within placement learning and providing constructive theological reflection upon that prior learning. This will bring great benefits to these institutions through their becoming re-connected and re-embedded in the life of the church at grass roots level, giving them a valued and indispensable role in the mission of the church in diverse contexts.
Differential Magnetometer Measurements of Geomagnetically Induced Currents in a Complex High Voltage Network
Authors: Hübert J. , Beggan C. D. , Richardson G. S. , Martyn T. , Thomson A. W. P.
Published: March 2020

Space weather poses a hazard to grounded electrical infrastructure such as high voltage (HV) transformers, through the induction of geomagnetically induced currents (GICs). Modeling GICs requires knowledge of the source magnetic field and the Earth's electrical conductivity structure, in order to calculate the geoelectric fields generated during magnetic storms, as well as knowledge of the topology of the HV network. Direct measurement of GICs at the ground neutral in substations is possible with a Hall effect probe, but such data are not widely available. To validate our HV network model, we use the differential magnetometer method (DMM) to measure GICs in the 400 kV grid of Great Britain. We present DMM measurements for the 26 August 2018 storm at a site in eastern Scotland with up to 20 A recorded. The line GIC correlates well with Hall probe measurements at a local transformer, though they differ in amplitude by an order of magnitude (a maximum of
2 A). We deployed a long‐period magnetotelluric (MT) instrument to derive the local impedance tensor which can be used to predict the geoelectric field from the recorded magnetic field. Using the MT‐derived electric field estimates, we model GICs within the network, accounting for the difference in magnitude between the DMM‐measured line currents and earth currents at the local substation. We find that the measured line and earth GICs match the expected GICs from our network model, confirming that detailed knowledge of the complex network topology and its resistance parameters is essential for accurately computing GICs.
D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration
Authors: Wang Bowen , Wang Li , Gu Sijie , Yu Yankun , Huang Huaxing , Mo Kunlun , Xu He , Zeng Fanzhu , Xiao Yichen , Peng Lulu , Liu Chunqiao , Cao Nan , Liu Yizhi , Yuan Jin , Ouyang Hong
Published: March 2020

Accumulated oxidative damage may lead to irreversible retinal pigmented epithelium (RPE) cell death, which is considered to be the primary cause of dry age-related macular degeneration (AMD), leading to blindness in the elderly. However, an effective therapy for this disease is lacking. Here, we described a robust high-content screening procedure with a library of 814 protective compounds and found that D609 strongly protected RPE cells from sodium iodate (SI)-induced oxidative cell death and prolonged their healthy survival. D609 effectively attenuated excessive reactive oxygen species (ROS) and prevented severe mitochondrial loss due to oxidative stress in the RPE cells. Surprisingly, the potent antioxidative effects of D609 were not achieved through its own reducibility but were primarily dependent on its ability to increase the expression of metallothionein. The injection of this small water-soluble molecule also showed an explicit protective effect of the RPE layer in an SI-induced AMD mouse model. These findings suggested that D609 could serve as a novel antioxidative protector of RPE cells both in vitro and in vivo and unveiled a novel antioxidative mechanism of D609, which may ultimately have clinical applications for the treatment of AMD.
Spatiotemporal dynamics of the archaeal community in coastal sediments: assembly process and co-occurrence relationship
Authors: Liu Jiwen , Zhu Shangqing , Liu Xiaoyue , Yao Peng , Ge Tiantian , Zhang Xiao-Hua
Published: March 2020

Studies of marine benthic archaeal communities are updating our view of their taxonomic composition and metabolic versatility. However, large knowledge gaps remain with regard to community assembly processes and inter taxa associations. Here, using 16S rRNA gene amplicon sequencing and qPCR, we investigated the spatiotemporal dynamics, assembly processes, and co-occurrence relationships of the archaeal community in 58 surface sediment samples collected in both summer and winter from across ∼1500 km of the eastern Chinese marginal seas. Clear patterns in spatiotemporal dynamics in the archaeal community structure were observed, with a more pronounced spatial rather than seasonal variation. Accompanying the geographic variation was a significant distance-decay pattern with varying contributions from different archaeal clades, determined by their relative abundance. In both seasons, dispersal limitation was the most important process, explaining ∼40% of the community variation, followed by homogeneous selection and ecological drift, that made an approximately equal contribution (∼30%). This meant that stochasticity rather than determinism had a greater impact on the archaeal community assembly. Furthermore, we observed seasonality in archaeal co-occurrence patterns: closer inter-taxa connections in winter than in summer, and unmatched geographic patterns between community composition and co-occurrence relationship. These results demonstrate that the benthic archaeal community was assembled under a seasonal-consistent mechanism but the co-occurrence relationships changed over the seasons, indicating complex archaeal dynamic patterns in coastal sediments of the eastern Chinese marginal seas.
The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm
Authors: Ramat Anne , Garcia-Silva Maria-Rosa , Jahan Camille , Naït-Saïdi Rima , Dufourt Jérémy , Garret Céline , Chartier Aymeric , Cremaschi Julie , Patel Vipul , Decourcelle Mathilde , Bastide Amandine , Juge François , Simonelig Martine
Published: March 2020

Piwi-interacting RNAs (piRNAs) and PIWI proteins are essential in germ cells to repress transposons and regulate mRNAs. InDrosophila, piRNAs bound to the PIWI protein Aubergine (Aub) are transferred maternally to the embryo and regulate maternal mRNA stability through two opposite roles. They target mRNAs by incomplete base pairing, leading to their destabilization in the soma and stabilization in the germ plasm. Here, we report a function of Aub in translation. Aub is required for translational activation ofnanosmRNA, a key determinant of the germ plasm. Aub physically interacts with the poly(A)-binding protein (PABP) and the translation initiation factor eIF3. Polysome gradient profiling reveals the role of Aub at the initiation step of translation. In the germ plasm, PABP and eIF3d assemble in foci that surround Aub-containing germ granules, and Aub acts with eIF3d to promotenanostranslation. These results identify translational activation as a new mode of mRNA regulation by Aub, highlighting the versatility of PIWI proteins in mRNA regulation.
Enhancing multiphoton upconversion through interfacial energy transfer in multilayered nanoparticles
Authors: Zhou Bin , Tang Bing , Zhang Chuang , Qin Changyun , Gu Zhanjun , Ma Ying , Zhai Tianyou , Yao Jiannian
Published: March 2020

Photon upconversion in lanthanide-doped upconversion nanoparticles offers a wide variety of applications including deep-tissue biophotonics. However, the upconversion luminescence and efficiency, especially involving multiple photons, is still limited by the concentration quenching effect. Here, we demonstrate a multilayered core-shell-shell structure for lanthanide doped NaYF4, where Er3+ activators and Yb3+ sensitizers are spatially separated, which can enhance the multiphoton emission from Er3+ by 100-fold compared with the multiphoton emission from canonical core-shell nanocrystals. This difference is due to the excitation energy transfer at the interface between activator core and sensitizer shell being unexpectedly efficient, as revealed by the structural and temperature dependence of the multiphoton upconversion luminescence. Therefore, the concentration quenching is suppressed via alleviation of cross-relaxation between the activator and the sensitizer, resulting in a high quantum yield of up to 6.34% for this layered structure. These findings will enable versatile design of multiphoton upconverting nanoparticles overcoming the conventional limitation.
Effects of chronic low-dose radiation on cataract prevalence and characterization in wild boar (Sus scrofa) from Fukushima, Japan
Authors: Pederson Samantha L. , Li Puma Margaret C. , Hayes Joshua M. , Okuda Kei , Reilly Christopher M. , Beasley James C. , Li Puma Lance C. , Hinton Thomas G. , Johnson Thomas E. , Freeman Kate S.
Published: March 2020

This study evaluated cataracts in wild boar exposed to chronic low-dose radiation. We examined wild boar from within and outside the Fukushima Exclusion Zone for nuclear, cortical, and posterior subcapsular (PSC) cataracts in vivo and photographically. Plausible upper-bound, lifetime radiation dose for each boar was estimated from radioactivity levels in each animal’s home range combined with tissue concentrations of 134+137Cesium. Fifteen exposed and twenty control boar were evaluated. There were no significant differences in overall prevalence or score for cortical or PSC cataracts between exposed and control animals. Nuclear (centrally located) cataracts were significantly more prevalent in exposed boar (p < 0.05) and had statistically higher median scores. Plausible upper-bound, lifetime radiation dose ranged from 1 to 1,600 mGy in exposed animals, with no correlation between dose and cortical or PSC score. While radiation dose and nuclear score were positively associated, the impact of age could not be completely separated from the relationship. Additionally, the clinical significance of even the highest scoring nuclear cataract was negligible. Based on the population sampled, wild boar in the Fukushima Exclusion Zone do not have a significantly higher prevalence or risk of cortical or PSC cataracts compared to control animals.
Absolute Structure from Scanning Electron Microscopy
Authors: Burkhardt Ulrich , Borrmann Horst , Moll Philip , Schmidt Marcus , Grin Yuri , Winkelmann Aimo
Published: March 2020

The absence of centrosymmetry in chiral and polar crystal structures is the reason for many technical relevant physical properties like optical birefringence or ferroelectricity. Other chirality related properties that are actually intensively investigated are unconventional superconductivity or unusual magnetic ordering like skyrmions in materials with B20 structure. Despite the often close crystal structure - property relation, its detection is often challenging due to superposition of domains with different absolute structure e.g. chirality. Our investigations of high quality CoSi crystals with B20 structure by both complementary methods X- ray (volume sensitive) and electron backscatter diffraction (EBSD) (surface sensitive) results the consistent assignment of the chirality and reveal fundamental differences in their sensitivity to chirality. The analysis of the surface of a CoSi crystal with domains of different chirality show the high spatial resolution of this method which opens the possibility to analyze the chirality in microstructures of technical relevant materials like thin films and catalysts.
Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients
Authors: de Miguel Pérez Diego , Rodriguez Martínez Alba , Ortigosa Palomo Alba , Delgado Ureña Mayte , Garcia Puche Jose Luis , Robles Remacho Agustín , Exposito Hernandez José , Lorente Acosta Jose Antonio , Ortega Sánchez Francisco Gabriel , Serrano Ma Jose
Published: March 2020

Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC.
High-throughput method for Antibiotic Susceptibility Testing based on Fluorescein Quenching by Bacteria: Application to Urinary Tract Infection
Authors: Radhakrishnan Rohit , J. Rajesh , N. S. Dinesh , C. P. Thangavelu , K. Sankaran
Published: March 2020

We recently reported a sugar-induced bacterial release of 13-Docosenamide and its ability to quench fluorescein. This simple handle to monitor bacterial growth is readily applicable to develop a quicker antibiotic sensitivity testing method along with a low-cost field-use optical instrumentation. Conditions were standardized to perform this new procedure in the most preferred and CLSI-recommended microdilution format in 12-well strips. A simple and portable optoelectronic prototype was used to capture the image and read the fluorescence signal of the culture medium of the 12-well strips. This new Fluorescence Quenching Method along with the device enabled the choice of the right antibiotic within 8 h of sample collection from the patient. It was compliant to the Clinical Laboratory Standard Institute’s quality control guidelines. Clinical assessment of the method using 440 urine samples from Urinary Tract Infection patients against 21 routinely used antibiotics showed a 94.3% match with the results of the Standard Disk Diffusion method. This new method saves the precious time taken for and the cost of antibiotic susceptibility testing for quicker and effective treatment with better compliance.
Dynamic changes of facial skeletal fractures with time
Authors: Yu Bao-Hai , Han Shu-Man , Sun Tao , Guo Zhe , Cao Lei , Wu Hui-Zhao , Shi Yun-Heng , Wen Jin-Xu , Wu Wen-Juan , Gao Bu-Lang
Published: March 2020

To investigate the characteristics of imaging changes with time of facial fractures, patients with facial fractures who had computed tomographic scan were enrolled including 500 patients who were divided into six groups based on the time of scanning: super early (<3 d), early (4–7 d), early-to-medium (8–14 d), medium (15–21d), medium-to-late (22d–2 months) and late stage (>2 months). The data were compared and analyzed. Forty two patients with frontal bone fractures had high-energy impact as the reason of fractures. The fracture line was clear and sharp within one week but blunt and sclerotic due to bone absorption at 2–3 weeks, and might exist for a long time. All patients had soft tissue swelling and paranasal sinus effusion at 1–2 weeks after injury. Air might gather in the adjacent soft tissues and/or intracranially within 3 days of injury if the fracture involved the frontal or other sinuses. Twelve of the 42 patients (28.6%) had intracranial hematoma, and five (11.9%) had epidural effusion. Subarachnoid hemorrhage was mostly absorbed within one week while epidural hematoma was completely absorbed over 3 weeks. Significant changes (P < 0.05) in the fracture lines, effusion of paranasal sinuses, soft tissue swelling and pneumocephalus were observed during the study period. For patients with medial orbital wall fractures, the fracture line was sharp and clear at early stages with concurrent sphenoid sinus effusion, and the fracture line became depressed 3 weeks later with disappearance of sphenoid sinus effusion. Significant changes (P < 0.05) were observed in the sharp fracture line, soft tissue swelling, sphenoid sinus effusion and smooth depression at fracture sites. For nasal fractures, the fracture line was sharp and clear at early stages with concurrent soft tissue swelling which disappeared one week later. The fracture line became smooth three weeks later. A significant (P < 0.05) difference was demonstrated in the changes of fracture line and soft tissue swelling with time. In conclusion, facial fractures have some dynamic alterations with time and identification of these characteristics may help reaching a correct clinical diagnosis with regard to fracture severity and time.
Oxidative stress enhanced the transforming growth factor-β2-induced epithelial-mesenchymal transition through chemokine ligand 1 on ARPE-19 cell
Authors: Yang I-Hui , Lee Jong-Jer , Wu Pei-Chang , Kuo Hsi-Kung , Kuo Yu-Hsia , Huang Hsiu-Mei
Published: March 2020

Fibroblast-like transformation of retinal pigment epithelial (RPE) cells is a pathological feature of proliferative vitreoretinopathy (PVR) that may cause blindness. The effect of oxidative stress alone or together with transforming growth factor-beta 2 (TGF-β2) on epithelial-mesenchymal transformation (EMT) is not fully understood in RPE. TGF-β2 induced the upregulation EMT markers including α-smooth muscle actin (α-SMA), Snail, and Slug and downregulation of E-cadherin (E-cad) in ARPE-19 cells. Hydrogen peroxide (H2O2) not only upregulated α-SMA but also enhanced the effect of TGF-β2 on the expression of Snail and Slug. The CXCL family of cytokines could be the mediators of EMT induced by H2O2 and TGF-β2. H2O2 induced CXCL1, that upregulated α-SMA and fibronectin. Both SB225002, an inhibitor of CXCR2, and antioxidant N-acetylcysteine suppressed the TGF-β2-induced EMT in ARPE-19 cells. Taken together, the results suggest that oxidative stress enhanced TGF-β2-induced EMT through the possible autocrine effect of CXCL1 on CXCR2 in ARPE-19 cells.
Pressurized carbon dioxide as a potential tool for decellularization of pulmonary arteries for transplant purposes
Authors: Gil-Ramírez Alicia , Rosmark Oskar , Spégel Peter , Swärd Karl , Westergren-Thorsson Gunilla , Larsson-Callerfelt Anna-Karin , Rodríguez-Meizoso Irene
Published: March 2020

Vascular bio-scaffolds produced from decellularized tissue offer a promising material for treatment of several types of cardiovascular diseases. These materials have the potential to maintain the functional properties of the extracellular matrix (ECM), and allow for growth and remodeling in vivo. The most commonly used methods for decellularization are based on chemicals and enzymes combinations, which often damage the ECM and cause cytotoxic effects in vivo. Mild methods involving pressurized CO2-ethanol (EtOH)-based fluids, in a supercritical or near supercritical state, have been studied for decellularization of cardiovascular tissue, but results are controversial. Moreover, data are lacking on the amount and type of lipids remaining in the tissue. Here we show that pressurized CO2-EtOH-H2O fluids (average molar composition, ΧCO2 0.91) yielded close to complete removal of lipids from porcine pulmonary arteries, including a notably decrease of pro-inflammatory fatty acids. Pressurized CO2-limonene fluids (ΧCO2 0.88) and neat supercritical CO2 (scCO2) achieved the removal of 90% of triacylglycerides. Moreover, treatment of tissue with pressurized CO2-limonene followed by enzyme treatment, resulted in efficient DNA removal. The structure of elastic fibers was preserved after pressurized treatment, regardless solvent composition. In conclusion, pressurized CO2-ethanol fluids offer an efficient tool for delipidation in bio-scaffold production, while pressurized CO2-limonene fluids facilitate subsequent enzymatic removal of DNA.
Author Correction: Deficient Insulin-mediated Upregulation of the Equilibrative Nucleoside Transporter 2 Contributes to Chronically Increased Adenosine in Diabetic Glomerulopathy
Authors: Alarcón Sebastián , Garrido Wallys , Vega Génesis , Cappelli Claudio , Suárez Raibel , Oyarzún Carlos , Quezada Claudia , Martín Rody San
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Identifying Severe Stroke Patients Likely to Benefit From Thrombectomy Despite Delays of up to a Day
Authors: González R. Gilberto , Silva Gisele Sampaio , He Julian , Sadaghiani Saloomeh , Wu Ona , Singhal Aneesh B.
Published: March 2020

Selected patients with large vessel occlusions (LVO) can benefit from thrombectomy up to 24 hours after onset. Identifying patients who might benefit from late intervention after transfer from community hospitals to thrombectomy-capable centers would be valuable. We searched for presentation biomarkers to identify such patients. Frequent MR imaging over 2 days of 38 untreated LVO patients revealed logarithmic growth of the ischemic infarct core. In 24 patients with terminal internal carotid artery or the proximal middle cerebral artery occlusions we found that an infarct core growth rate (IGR) <4.1 ml/hr and initial infarct core volumes (ICV) <19.9 ml had accuracies >89% for identifying patients who would still have a core of <50 ml 24 hours after stroke onset, a core size that should predict favorable outcomes with thrombectomy. Published reports indicate that up to half of all LVO stroke patients have an IGR <4.1 ml/hr. Other potentially useful biomarkers include the NIHSS and the perfusion measurements MTT and Tmax. We conclude that many LVO patients have a stroke physiology that is favorable for late intervention, and that there are biomarkers that can accurately identify them at early time points as suitable for transfer for intervention.
Aerobic and anaerobic removal of lead and mercury via calcium carbonate precipitation mediated by statistically optimized nitrate reductases
Authors: Eltarahony Marwa , Zaki Sahar , Abd-El-Haleem Desouky
Published: March 2020

The nonbiodegradability nature of heavy metals renders them resident in food chain and subsequently, destructing the entire ecosystem. Therefore, this study aimed to employ nitrate reduction-driven calcium carbonate precipitation in remediation of lead and mercury aerobically and anaerobically by Proteus mirabilis 10B, for the first time. Initially, Plackett-Burman design was employed to screen of 16 independent variables for their significances on periplasmic (NAP) and membrane-bound (NAR) nitrate reductases. The levels for five significant variables and their interaction effects were further optimized by central composite design. The maximum activities of NAP and NAR recorded 2450 and 3050 U/mL by 2-fold enhancement, comparing with non-optimized medium. Under aerobic and anaerobic optimized remediation conditions, the changes in media chemistry revealed positive correlation among bacterial growth, nitrate reductase activity, pH, NO3− and NO2− consumption and removal of Ca2+, Pb2+ and Hg2+. Subsequently, the remediated precipitates were subjected to mineralogical analysis; energy dispersive X-ray patterns exhibited characteristic peaks of C, O and Ca in addition to Pb and Hg. Scanning electron microscope depicted the presence of bacterial imprints and protrusions on rough and smooth surface bioliths. However, X-ray diffraction indicated entrapment of PbCO3, Pb2O, CaPbO3, Hg and Hg2O in calcite lattice. Interestingly, such approach is feasible, efficient, cost-effective and ecofriendly for heavy metals remediation.
Exploring the association of Bone Alkaline Phosphatases And Hearing Loss
Authors: Lim Zhu Wei , Chen Wei-Liang
Published: March 2020

Hearing loss becomes increasingly common with age and affects quality of life. Recently, scientists have published articles about the relationship between metabolic disease and hearing loss. Metabolic disease was previously found to be highly related to an increase in alkaline phosphatase. Thus, there may be an indirect relationship between alkaline phosphatase (ALP) and hearing loss. In this paper, we will demonstrate the relationship between ALP and hearing loss. We included 3877 National Health and Nutrition Examination Survey (NHANES) participants, who represent the noninstitutionalized civilian population in the United States from age 20 to age 69, and examined the association between ALP and frequency distributions of pure-tone air-condition (PTAC) thresholds. After adjusting for pertinent variables, the subjects who belonged to the higher quartiles of ALP tended to have worse hearing thresholds (pure tone average at high and low frequencies) than the first quartile of ALP (p < 0.001). The results showed a positive correlation between ALP and hearing loss, in both males and females (p < 0.001) and in subjects whose body mass indices (BMI) were less than 30 (p < 0.001). In conclusion, ALP may play a role in detecting hearing loss.
Long-term Outcome of Neurological Complications after Infective Endocarditis
Authors: Chen Ching-Chang , Wu Victor Chien-Chia , Chang Chien-Hung , Chen Chun-Ting , Hsieh Po-Chuan , Liu Zhuo-Hao , Wong Ho-Fai , Yang Chia-Hung , Chou An-Hsun , Chu Pao-Hsien , Chen Shao-Wei
Published: March 2020

Severe neurological complications following infective endocarditis remain a major problem with high mortality rate. The long-term neurological consequences following infective endocarditis remain uncertain. Otherwise, neurosurgeries could be performed after these complications; however, few clinical series have reported the results. Therefore, we utilized a large, nationwide database to unveil the long-term mortality and neurosurgical outcome following infective endocarditis. We included patients with a first-time discharge diagnosis of infective endocarditis between January 2001 and December 2013 during hospitalization. Patients were further divided into subgroups consisting of neurological complications under neurosurgical treatment and complications under non-neurosurgical treatment. Long-term result of symptomatic neurological complications after infective endocarditis and all-cause mortality after different kinds of neurosurgeries were analyzed. There were 16,495 patients with infective endocarditis included in this study. Symptomatic neurological complications occurred in 1,035 (6.27%) patients, of which 279 (26.96%) accepted neurosurgical procedures. Annual incidence of neurological complications gradually increased from 3.6% to 7.4% (P < 0.001). The mortality rate among these patients was higher than that among patients without complications (48.5% vs. 46.1%, P = 0.012, increased from 20% initially to nearly 50% over the 5-year follow-up). However, neurosurgery had no effect on the long-term mortality rate (50.9% vs. 47.6%, P = 0.451). Incidence of neurological complications post-infective endocarditis is increasing, and patients with these complications have higher mortality rates than patients without. Neurosurgery in these populations was not associated with higher long-term mortality. Therefore, it should not be ruled out as an option for those with neurological complications.
Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation
Authors: Abu-rish Eman Y. , Mansour Ahmad T. , Mansour Hebah T. , Dahabiyeh Lina A. , Aleidi Shereen M. , Bustanji Yasser
Published: March 2020

Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these conditions. However, little is known about its immunomodulatory effects on cytokine secretionin vivoandin vitro. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB onin vivoandin vitroIL-1β, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytesin vitro.In vivo, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1β and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions.
Intrinsically p-type cuprous iodide semiconductor for hybrid light-emitting diodes
Authors: Ahn D. , Song J. D. , Kang S. S. , Lim J. Y. , Yang S. H. , Ko S. , Park S. H. , Park S. J. , Kim D. S. , Chang H. J. , Chang Joonyeon
Published: March 2020

Cuprous halides, characterized by a direct wide band-gap and a good lattice matching with Si, is an intrinsic p-type I-VII compound semiconductor. It shows remarkable optoelectronic properties, including a large exciton binding energy at room temperature and a very small piezoelectric coefficient. The major obstacle to its application is the difficulty in growing a single-crystal epitaxial film of cuprous halides. We first demonstrate the single crystal epitaxy of high quality cuprous iodide (CuI) film grown on Si and sapphire substrates by molecular beam epitaxy. Enhanced photoluminescence on the order of magnitude larger than that of GaN and continuous-wave optically pumped lasing were found in MBE grown CuI film. The intrinsic p-type characteristics of CuI were confirmed using an n-AlGaN/p-CuI junction that emits blue light. The discovery will provide an alternative way towards highly efficient optoelectronic devices compatible with both Si and III-nitride technologies.