bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular mechanisms underlying temperature-induced bleaching in the tropical sea anemone Aiptasia pulchella
Authors: Sawyer Sara J. , Muscatine Leonard
Published: April 2021

Temperature-induced bleaching in symbiotic cnidarians is a result of the detachment and loss of host cells containing symbiotic algae. We tested the hypothesis that host cell detachment is evoked through a membrane thermotropic event causing an increase in intracellular calcium concentration, [Ca2+]i, which could then cause collapse of the cytoskeleton and perturb cell adhesion. Electron paramagnetic resonance measurements of plasma membranes from the tropical sea anemone Aiptasia pulchella and the Hawaiian coral Pocillopora damicornis labeled with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) revealed no membrane thermotropic event. In addition, intracellular imaging using Fura-2AM as well as labeling anemones with 45Ca revealed no significant change in [Ca2+]i. However, bleaching could be evoked at ambient temperature with 25 mmol l–1 caffeine without affecting [Ca2+]i. [Ca2+]i could be altered with ionomycin in isolated host cells, but ionomycin could not induce bleaching in A. pulchella. As caffeine can affect levels of intracellular protein phosphorylation, the ability of other agents that alter intracellular levels of protein phosphorylation to evoke bleaching was investigated. The protein phosphatase inhibitor vanadate could induce bleaching in A. pulchella. Two-dimensional gels of 32P-labeled proteins from cold-shocked, caffeine-treated and control anemones show that both temperature shock and caffeine alter the array of phosphorylated host soluble proteins. We conclude that cnidarian bleaching is linked to a temperature-induced alteration in protein phosphorylation.
Alternative splicing, muscle contraction and intraspecific variation: associations between troponin T transcripts, Ca2+ sensitivity and the force and power output of dragonfly flight muscles during oscillatory contraction
Authors: Marden James H. , Fitzhugh Gail H. , Girgenrath Mahasweta , Wolf Melisande R. , Girgenrath Stefan
Published: April 2021

The flight muscles of Libellula pulchella dragonflies contain a mixture of six alternatively spliced transcripts of a single troponin T (TnT) gene. Here, we examine how intraspecific variation in the relative abundance of different TnT transcripts affects the Ca2+ sensitivity of skinned muscle fibers and the performance of intact muscles during work-loop contraction regimes that approximate in vivo conditions during flight. The relative abundance of one TnT transcript, or the pooled relative abundance of two TnT transcripts, showed a positive correlation with a 10-fold range of variation in Ca2+ sensitivity of skinned fibers (r2=0.77, P<0.0001) and a threefold range in peak specific force (r2=0.74, P<0.0001), specific work per cycle (r2=0.54; P<0.0001) and maximum specific power output (r2=0.48, P=0.0005) of intact muscle. Using these results to reanalyze previously published data for wing kinematics during free flight, we show that the relative abundances of these particular transcripts are also positively correlated with wingbeat frequency and amplitude. TnT variation alone may be responsible for these effects, or TnT variation may be a marker for changes in a suite of co-regulated molecules. Dragonflies from two ponds separated by 16 km differed significantly in both TnT transcript composition and muscle contractile performance, and within each population there are two distinct morphs that showed different maturational trajectories of TnT transcript composition and muscle contractility. Thus, there is broad intraspecific variability and a high degree of population structure for contractile performance phenotypes, TnT ribotypes and ontogenetic patterns involving these traits that affect locomotor performance.
Techniki rejestracji zdalnej w kartowaniu geomorfologicznym wybrzeży klifowych
Authors: Winowski Marcin
Published: April 2021

This paper presents the evaluation of three remote sensing methods used in geomorphological mapping of cliff coasts. The basic parameters of point clouds obtained in the process of airborne laser scanning (ALS), terrestrial laser scanning (TLS) and digital processing of photos obtained with UAV (Structure from Motion – UAV-SfM) were analysed. The obtained results allowed to state that the models with the highest resolution and accuracy can be obtained using the TLS and UAV-SfM methods. These two techniques provide the greatest possibilities in detailed relief analyses and estimation of the sediment budget in small research sites. Images of ALS are less accurate, but for studies carried out in larger areas they seem to be the most optimal solution.
The hydrological role of biological topsoil crusts and water repellency in sandy dry-land areas
Authors: Yair Aaron , Almog Ram , Arbel Youval
Published: April 2021

Dryland areas are regarded as highly sensitive to climatic changes. A positive relationship between rainfall and environmental factors is often assumed for areas with an average annual rainfall of 100–300 mm. This assumption disregards the fact that a climate change in arid areas is not limited to climatic factors. It is often accompanied by a pronounced spatial variability in surface characteristics. The present work deals with the complex relationships among average annual rainfall, surface properties and the spatial redistribution of water resources in sandy areas located in the Northern Negev Desert. Two case studies are considered. The first deals with the hydrological effects of biological topsoil crusts on the water regime, along a rainfall gradient (86–170 mm). This study is based on five monitoring sites. Data obtained show a decrease in water availability with increasing annual rainfall. The findings are attributed to the decisive role played by the non-uniform properties of the topsoil crust along the rainfall gradient. The second case refers to the non-uniform development, and survival, of planted trees. Trees planted on steep dunes are well developed, with a high survival rate, whereas trees planted on low angle dunes are small. This study focused on the role of a water repellent layer on the water regime. Data obtained show a striking difference between steep and low dunes in all aspects studied, namely the degree of water repellency, frequency and magnitude of runoff events, infiltration depth and soil moisture. All variables monitored were found higher on steep than on low dunes. The large trees shed a substantial amount of leaves, whose decay developed a water repellent layer. Runoff generation over the repellent layer enhanced deep water penetration, through the process of subsurface flow. The lack of a water repellent layer over the low dunes prevented runoff generation, with its positive effects.
Update on Tail biting in pigs: An undesirable damaging behaviour
Authors: KAKANIS M , SOSSIDOU EN , KRITAS SK , TZIKA ED
Published: April 2021

Tail-biting is an abnormal behavior of multifactorial origin, that consists a major problem in modern pig industry. It has a serious impact on both welfare and health status of the pigs involved, as well as on economic profitability of the farm. It is considered to be a problem of pig adaptation in poor environment triggered by a plethora of external and internal risk factors interacting with each other. A great variation exists on prevalence of tail biting between different studies across the world. Tail docking is the common practice applied by farmers to prevent this behavior, while treatments are based on enrichment material provision. The aim of this review is to explore the most recent literature on risk factors and impacts of tail biting and to discuss promising areas on early prediction and treatment of the topic.
Assessment of oxidative stress, trace elements, serum biochemistry, and hormones levels in weaned calves with dermatophytosis
Authors: SEZER K , HANEDAN B , OZCELIK M , KIRBAS A
Published: April 2021

In this study, it was aimed to evaluate oxidative stress, serum biochemistry, trace elements, minerals, and testosterone and thyroid hormone levels in weaned calves with dermatophytosis. A total of 28 weaned Holstein calves were used in the study, including 6-8 months old, 14 with dermatophytosis (7 males, 7 females) and 14 healthy (7 males, 7 females). The animals were grouped as the diseased and healthy animals, 14 animals in each group as well as the male diseased and the male healthy animals were grouped as 7 animals in each group for the comparison of testosterone levels. The blood analyses were performed using ELISA kits and biochemistry automatic analyzer. There was a significant difference between the diseased and healthy groups for NO (nitric oxide) (P<0.05), TOS (total oxidative stress) (P<0.001), TAC (total antioxidant capacity) (P<0.01). However, in comparison of the diseased and healthy groups, serum biochemistry with the exception of glucose and triglyceride,trace elements except for manganese, minerals, and thyroid hormone levels were not statistically different (P>0.05). In comparison of the diseased and healthy animals for testosterone levels, it was not determined any difference (P>0.05). The present study revealed that dermatophytosis could affect oxidant status in calves with dermatophytosis, and that TOC (total oxidant capacity) and NO as oxidative stress marker might be increased for fungicidal effect in the diseased animals with dermatophytosis.
Mass mortality of unknown etiology in alpine newts (Ichtyosaura alperstris veluchiensis) in an alpine lake in Greece
Authors: AZMANIS PN , SCHMIDT V , SAINIS I , MARSCHANG RE , PAPAIOANNOU H
Published: April 2021

A mass mortality in alpine newts (Ichthyosaura alpestris veluchiensis) was observed in May/June 2013, in Drakolimni lake on Smolikas Mountain, Northwest Greece. 1300 alpine newts were found dead in two events. In 1998 a similar incident was recorded in the nearby lake of Timfi Mt. Newts of every stage and sex were affected, presenting incoordination and inability to float evenly. Ten animals were submitted for complete pathological examination. Field environmental measurements (water temperature, oxygen saturation, pH, conductance, nitric/phosphate concentration) and samples (water, snow, benthos) were collected for ecotoxicological and quality analysis. Necropsy, microbiology (parasitology, bacteriology, mycology), histopathology, molecular investigations (Ranavirus spp, Batrachochytridium dendrobatidis, Batrachochytridium salamandrivorans), quality and ecotoxicological examinations did not indicate a causative source for the mortality. To the author´s knowledge this is the biggest mortality of unknown etiology reported in free-living alpine newts in Europe.
Survival of Shiga Toxin-Producing Escherichia coli (STEC) Serogroups During Production and Storage of Yogurt
Authors: CELIK G , DIKICI A , KOLUMAN A
Published: April 2021

In this study, the survival of Escherichia coli O157:H7 and non-O157 STEC serogroups of O26, O111, O103, and O145 were investigated during production and storage of yogurt. For this purpose, pathogens were individually inoculated into milk after pasteurization along with the starter culture (approximately 7.00±1.00 log10 cfu/g). After incubation at 44oC (about 180 min), yogurt samples were capped and stored at 4oC for 20 days. Pathogens were enumerated at 0, 5, 10, 15, and 20th days of storage. Lactic acid content (%) and pH of the samples were also screened. Moreover, mesophilic Lactococcus spp. and mesophilic Lactobacillus spp. were enumerated during production of yogurt.After incubation, the number of E. coli O157, O26, O103, O145, O111were 6.76±0.45, 6.64±0.53, 7.12±0.43, 6.00±1.39, 5.89±1.37 log10 cfu/g, respectively. A significant decrease was determined in all groups during the storage of yogurt samples at 4oC (p<0.05). It was detected on the 20th day of storage that the number of E. coli O157:H7 and non-O157 STEC serogroups of O103 and O145 were under the detection limit. However, STEC O26 and O111 were viable around 1.51±0.98 and 1.18±0.62 log10 cfu/g respectively. Results of the study showed that Escherichia coli O157:H7 and non-O157 STEC serogroups might pose a potential health risk during production and storage of yogurt.
Data Management Plans in Horizon 2020: what beneficiaries think and what we can learn from their experience
Authors: Spichtinger Daniel
Published: April 2021

Background: Data Management Plans (DMPs) are at the heart of many research funder requirements for data management and open data, including the EU’s Framework Programme for Research and Innovation, Horizon 2020. This article provides a summary of the findings of the DMP Use Case study, conducted as part of OpenAIRE Advance.

Methods: As part of the study we created a vetted collection of over 800 Horizon 2020 DMPs. Primarily, however, we report the results of qualitative interviews and a quantitative survey on the experience of Horizon 2020 projects with DMPs.

Results & Conclusions: We find that a significant number of projects had to develop a DMP for the first time in the context of Horizon 2020, which points to the importance of funder requirements in spreading good data management practices. In total, 82% of survey respondents found DMPs useful or partially useful, beyond them being “just” an European Commission (EC) requirement. DMPs are most prominently developed within a project’s Management Work Package. Templates were considered important, with 40% of respondents using the EC/European Research Council template. However, some argue for a more tailor-made approach. The most frequent source for support with DMPs were other project partners, but many beneficiaries did not receive any support at all. A number of survey respondents and interviewees therefore ask for a dedicated contact point at the EC, which could take the form of an EC Data Management Helpdesk, akin to the IP helpdesk. If DMPs are published, they are most often made available on the project website, which, however, is often taken offline after the project ends. There is therefore a need to further raise awareness on the importance of using repositories to ensure preservation and curation of DMPs. The study identifies IP and licensing arrangements for DMPs as promising areas for further research.
Weaning wisely
Authors: Rawstrone Annette
Published: April 2021

What does weaning really mean and what is the best way to approach it? Annette Rawstrone provides practical, common sense advice in the first of a new series covering early development stages.
Aproximación empírica al Programa Erasmus... ¿Fomenta la competencia Europeísta?
Authors: Asenjo Gomez Juan Tomás , Urosa Sanz Belén Mercedes , Valle López Javier Manuel
Published: April 2021

INTRODUCCIÓN. El programa de movilidad académica Erasmus ya ha cumplido 30 años desde su puesta en marcha (1987). Con una imagen de éxito tanto en cifras como en su aportación al fortalecimiento de una ciudadanía europea, se ha convertido en un referente para cualquier universitario. La aceptación popular de su efecto positivo contrasta con el reducido número de investigaciones empíricas que comprueban si este programa realmente contribuye a la mejora del europeísmo. MÉTODO. Para tal fin se contó con el Cuestionario de Competencia Europeísta que analiza este constructo desde la consideración de las dimensiones de conocimientos, destrezas y actitudes que lo componen. Con una muestra de 157 estudiantes universitarios se llevó a cabo un estudio cuasiexperimental con grupos los Experimental y Control con medidas pre y posmovilidad. Se realizaron análisis de varianza de dos factores para el estudio de los efectos principales de la realización o no de la experiencia Erasmus (intersujeto) y el tiempo trascurrido entre las medidas pre y pos (intrasujeto), así como la interacción entre ambas fuentes de variabilidad sobre las dimensiones del constructo. RESULTADOS. Los resultados mostraron diferencias significativas en estas dimensiones a favor del alumnado que realiza la experiencia Erasmus. Sin embargo, no se pudieron encontrar diferencias significativas entre las medidas pre-pos, ni se demostró la existencia de interacción. DISCUSIÓN. A pesar de que no se aprecian cambios significativos tras la movilidad, la investigación realizada está ceñida a un espacio de tiempo muy concreto, circunstancia que condiciona evaluar un constructo tan complejo como el identitario. Se requiere un análisis a más largo plazo para comprender las bondadesasociadas al programa Erasmus, avalado por más de diez millones de beneficiarios en los últimos treinta años. De la misma manera, es ineludible una visión holística de los beneficios personales y sociales resultantes.
Exentos de la fiscalidad del General en el Reino de Valencia. La reivindicación de inmunidad por el clero regular.
Authors: Canet Aparisi Teresa
Published: April 2021

Les relacions entre la Generalitat valenciana i el clergat regular experimentaren fortes tensions al segle XVII amb motiu de l’exempció fiscal dels eclesiàstics, especialment els mendicants. L’anàlisi d’aquests conflictes ens permet apropar-nos a la realitat efectiva d’un privilegi fiscal poc conegut en la seua incidència i derivacions.
Constantia et clementia. El lenguaje de la gracia real en cuatro ciudades en rebeldía Quito, México, Nápoles, Barcelona (1592-1652).
Authors: Bautista y Lugo Gibran
Published: April 2021

L’article posa en relleu els aspectes comuns del llenguatge de la gràcia reial en la monarquia hispana com a mecanisme de compensació en ciutats en rebel·lia, així com les particularitats de l’exercici que en van fer diversos tipus de mediadors, a partir de la comparació de quatre casos ocorreguts entre el 1592 i el 1653. S’examinen els escenaris de conflicte i les dinàmiques de reincorporació; els elements convencionals de la clemència règia formulats a partir de la intervenció d’autoritats, grups rebels i mediadors; les graduacions en què es formulava la gràcia real, des del perdó selectiu fins a la nul·litat general, i els seus efectes perlocutius com a instrument detonant de fòrums de negociació.
Introduction "Iberia, the Mediterranean and the larger world in the late medieval and early modern periods".
Authors: Barton Thomas W. , Kelleher Marie A. , Zaldívar Antonio M.
Published: April 2021

Introducció al dossier "Iberia, the Mediterranean and the larger world in the late medieval and early modern periods".
Generation of needle beams through focusing of azimuthally polarized vortex beams by polarization-insensitive metasurfaces
Authors: Shen Zhe , Li Rui , Huang Shijie , Zhang Baifu , Chen Qinnan
Published: April 2021

Needle beams are widely used in advanced applications due to their high intensity, high resolution, and extended depth of focus. In this work, the generation of needle beams through transmitting azimuthally polarized beams to polarization-insensitive metasurfaces is presented. Defocus phase profiles and annular apertures were adopted to obtain needle beams, respectively. A relatively long depth of focus (

16.9

λ

) with subdiffraction beam size (

0.41

λ

) was obtained. The introduction of metasurfaces can significantly simplify an optical system compared with traditional methods utilizing complex optical elements. This study may contribute to photolithography, microscopy, particle manipulation, and acceleration.
Efficient spontaneous emission by metal-dielectric antennas; antenna Purcell factor explained
Authors: Hooten Sean , Andrade Nicolas M. , Wu Ming C. , Yablonovitch Eli
Published: April 2021

The rate of spontaneous emission from an optical emitter can be greatly enhanced using a metallic optical antenna at the penalty of efficiency. In this paper we propose a metal-dielectric antenna that eliminates the tradeoff between spontaneous emission enhancement and radiative efficiency by using nanoscopic dielectric structures at the antenna tips. This tradeoff occurs due to Ohmic loss and is further exacerbated by electron surface collisions. We find that our metal-dielectric antenna can enhance spontaneous emission by a factor 5 × 105 with efficiency = 70%, greatly exceeding the radiative efficiency of a purely metallic antenna with similar enhancement. Moreover, the metal-dielectric antenna design strategy is naturally amenable to short-distance optical communications applications. We go on to discuss the Purcell effect within the context of antenna enhancement. Metallic optical antennas are best analyzed with conventional antenna circuit models, but if the Purcell enhancement were to be employed, we provide the effective mode volume, Veff = (3/4π2)2 d2λ(λ/l)5, that would be needed.
Two-step training deep learning framework for computational imaging without physics priors
Authors: Shang Ruibo , Hoffer-Hawlik Kevin , Wang Fei , Situ Guohai , Luke Geoffrey P.
Published: April 2021

Deep learning (DL) is a powerful tool in computational imaging for many applications. A common strategy is to use a preprocessor to reconstruct a preliminary image as the input to a neural network to achieve an optimized image. Usually, the preprocessor incorporates knowledge of the physics priors in the imaging model. One outstanding challenge, however, is errors that arise from imperfections in the assumed model. Model mismatches degrade the quality of the preliminary image and therefore affect the DL predictions. Another main challenge is that many imaging inverse problems are ill-posed and the networks are over-parameterized; DL networks have flexibility to extract features from the data that are not directly related to the imaging model. This can lead to suboptimal training and poorer image reconstruction results. To solve these challenges, a two-step training DL (TST-DL) framework is proposed for computational imaging without physics priors. First, a single fully-connected layer (FCL) is trained to directly learn the inverse model with the raw measurement data as the inputs and the images as the outputs. Then, this pre-trained FCL is fixed and concatenated with an un-trained deep convolutional network with a U-Net architecture for a second-step training to optimize the output image. This approach has the advantage that does not rely on an accurate representation of the imaging physics since the first-step training directly learns the inverse model. Furthermore, the TST-DL approach mitigates network over-parameterization by separately training the FCL and U-Net. We demonstrate this framework using a linear single-pixel camera imaging model. The results are quantitatively compared with those from other frameworks. The TST-DL approach is shown to perform comparable to approaches which incorporate perfect knowledge of the imaging model, to be robust to noise and model ill-posedness, and to be more robust to model mismatch than approaches which incorporate imperfect knowledge of the imaging model. Furthermore, TST-DL yields better results than end-to-end training while suffering from less overfitting. Overall, this TST-DL framework is a flexible approach for image reconstruction without physics priors, applicable to diverse computational imaging systems.
Two-beam coupling in the production of quantum correlated images by four-wave mixing
Authors: Wu Meng-Chang , Brewer Nicholas R. , Speirs Rory W. , Jones Kevin M. , Lett Paul D.
Published: April 2021

We investigate the effect of 2-beam coupling in different imaging geometries in generating intensity-difference squeezing from four-wave mixing (4WM) in Rb atomic vapors. A recently-introduced dual-seeding technique can cancel out the classical noise in a seeded four-wave mixing process. This dual-seeding technique, however, can introduce new complications that involve 2-beam coupling between different seeded spatial modes in the atomic vapor and can ruin squeezing at frequencies on the order of the atomic linewidth and below. This complicates some forms of quantum imaging using these systems. Here we show that seeding the 4WM process with skew rays can eliminate the excess noise caused by 2-beam coupling. To avoid 2-beam coupling in bright, seeded images, it is important to re-image the object in the gain medium, instead of focussing through it.
Broadband chiral silicon photonic circuits based on fork-type inversely tapered nanowire waveguides
Authors: Fang Liang , Wang Jian
Published: April 2021

Optical spin or circular polarization provides a new degree of freedom to control light–matter interaction in the fundamentals and applications of light. To broaden the bandwidth of chiral (spin-controlled) coupling in photonic integrated circuits, we propose fork-type inversely tapered nanowire waveguides to compensate for the out-of-step phase evolution of adiabatic coupling between

T
E

0

and

T
M

0

(

T
E

1

) modes excited from the

x

- and

y

-polarization components of spin polarized light in free space, respectively. We design and simulate two kinds of devices based on air and

S
i

3

N

4

up-claddings to show the feasibility of broadening the bandwidth of chiral silicon photonic circuits by using fork-type inverse tapers. Numerical results show that the bandwidth can approach 70 nm under high directionality of above 0.90. This broadband chiral coupling via the new phase synchronizing technique with fork-type inverse tapers may pave the way to develop on-chip spin photonics or polarization-based photonic integrated devices.
Characterization of NADH fluorescence properties under one-photon excitation with respect to temperature, pH, and binding to lactate dehydrogenase
Authors: Cannon Taylor M. , Lagarto Joao L. , Dyer Benjamin T. , Garcia Edwin , Kelly Douglas J. , Peters Nicholas S. , Lyon Alexander R. , French Paul M. W. , Dunsby Chris
Published: April 2021

Reduced nicotinamide adenine dinucleotide (NADH) is the principal electron donor in glycolysis and oxidative metabolism and is thus recognized as a key biomarker for probing metabolic state. While the fluorescence characteristics of NADH have been investigated extensively, there are discrepancies in the published data due to diverse experimental conditions, instrumentation and microenvironmental parameters that can affect NADH fluorescence. Using a cuvette-based time-resolved spectrofluorimeter employing one-photon excitation at 375 nm, we characterized the fluorescence intensity, lifetime, spectral response, anisotropy and time-resolved anisotropy of NADH in aqueous solution under varying microenvironmental conditions, namely temperature, pH, and binding to lactate dehydrogenase (LDH). Our results demonstrate how temperature, pH, and binding partners each impact the fluorescence signature of NADH and highlight the complexity of the fluorescence data when different parameters produce competing effects. We hope that the data presented in this study will provide a reference for potential sources of variation in experiments measuring NADH fluorescence.
Application of DNA barcodes and spatial analysis in conservation genetics and modeling of Iranian Salicornia genetic resources
Authors: Zeinalabedini Mehrshad , Khoshkholgh Sima Nayer Azam , Ghaffari Mohammad Reza , Ebadi Ali , Farsi Maryam
Published: April 2021

Iran is one of the origins of someSalicorniaspecies. Nevertheless, comprehensive research has not been conducted on genetic potential, distribution, selection of populations, and the economic utilization ofSalicorniain Iran. In the current study,Salicorniawas collected based on the previous data available for 26 different geographical locations of provinces in Iran. We examined Salicornia plants’ universality DNA barcodes, including rbcL, matK, trnH-psbA, and ITS, and their species identification abilities and identified six species groups. Subsequently, accurate modeling of distributed areas was provided with MAXENT and highlighted the valuable information on the diversity of specific geographical regions, conservation status of existing species, prioritization of conservation areas, and selection of Agro-Ecological areas. Together, this type of integrative study will provide useful information for managing and utilizingSalicorniagenetic resources in Iran.
Drug shortage management: A qualitative assessment of a collaborative approach
Authors: Chen Emily , Goold Susan , Harrison Sam , Ali Iman , Makki Ibtihal , Kent Stanley S. , Shuman Andrew G.
Published: April 2021

Drug shortages frequently and persistently affect healthcare institutions, posing formidable financial, logistical, and ethical challenges. Despite plentiful evidence characterizing the impact of drug shortages, there is a remarkable dearth of data describing current shortage management practices. Hospitals within the same state or region may not only take different approaches to shortages but may be unaware of shortages proximate facilities are facing. Our goal is to explore how hospitals in Michigan handle drug shortages to assess potential need for comprehensive drug shortage management resources. We conducted semi-structured interviews with diverse stakeholders throughout the state to describe experiences managing drug shortages, approaches to recent shortages, openness to inter-institutional engagement, ideas for a shared resource, and potential obstacles to implementation. To solicit additional feedback on ideas for a shared resource gathered from the interviews, we held focus groups with pharmacists, physicians, ethicists, and community representatives. Among participants representing a heterogeneous sample of institutions, three themes were consistent: (1) numerous drug shortage strategies occurring simultaneously; (2) inadequate resources and lead time to proactively manage shortages; and (3) interest in, but varied attitudes toward, a collaborative approach. These data provide insight to help develop and test a shared drug shortage management resource for enhancing fair allocation of scarce drugs. A shared resource may help institutions adopt accepted best practices and more efficiently access or share finite resources in times of shortage.
Unexpected distribution of the 4-formylaminooxyvinylglycine (FVG) biosynthetic pathway in Pseudomonas and beyond
Authors: Davis Edward W. , Okrent Rachel A. , Manning Viola A. , Trippe Kristin M.
Published: April 2021

The biological herbicide and antibiotic 4-formylaminooxyvinylglycine (FVG) was originally isolated from several rhizosphere-associated strains ofPseudomonas fluorescens. Biosynthesis of FVG is dependent on thegvgbiosynthetic gene cluster inP.fluorescens. In this investigation, we used comparative genomics to identify strains with the genetic potential to produce FVG due to presence of agvggene cluster. These strains primarily belong to two groups ofPseudomonas,P.fluorescensandP.syringae, however, a few strains with thegvgcluster were found outside ofPseudomonas. Mass spectrometry confirmed that all tested strains of theP.fluorescensspecies group produced FVG. However,P.syringaestrains did not produce FVG under standard conditions. Several lines of evidence regarding the transmission of thegvgcluster including a robust phylogenetic analysis suggest that it was introduced multiple times through horizontal gene transfer within thePseudomonaslineage as well as in select lineages ofThiomonas,BurkholderiaandPantoea. Together, these data broaden our understanding of the evolution and diversity of FVG biosynthesis. In the course of this investigation, additional gene clusters containing only a subset of the genes required to produce FVG were identified in a broad range of bacteria, including many non-pseudomonads.
Association between in-stent neointimal characteristics and native coronary artery disease progression
Authors: Jung Hae Won , Lim Chewan , Bae Han Joon , Lee Jung-Hee , Lee Yong-Joon , Kim Jung-Sun , Lee Seung-Jun , Hong Sung-Jin , Ahn Chul-Min , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo
Published: April 2021

Background and aims

The prognosis of stented lesions differs according to in-stent neointimal characteristics on optical coherence tomography (OCT). In particular, patients who show in-stent heterogeneous neointima are associated with a higher incidence of target lesion revascularization (TLR) compared with those who show in-stent non-heterogeneous neointima. However, the relationship between in-stent neointimal characteristics and native coronary atherosclerosis progression has not been clearly elucidated. The study aimed to investigate the relationship between in-stent neointimal characteristics and progression of native atherosclerosis.

Methods

The neointimal characteristics of 377 patients with 377 drug-eluting stents (DESs) were quantitatively and qualitatively assessed using OCT. The OCT-based neointima was categorized as homogeneous (n = 207), heterogeneous (n = 93), and layered (n = 77). The relationship of non-target lesion revascularization (non-TLR) with neointimal characteristics was evaluated after OCT examination of the stents.

Results

After a median follow-up duration of 40.0 months, patients with heterogeneous neointima showed significantly higher non-TLR rates than those with homogeneous neointima and tended to have higher non-TLR rates than those with layered neointima (heterogeneous vs. homogeneous:14.0% vs. 8.7%, p = 0.046; heterogeneous vs. layered neointima:14.0% vs. 7.8%, p = 0.152). Multivariate analysis showed that the independent determinants for non-TLR were heterogeneous neointima (HR: 2.237, 95% CI: 1.023–4.890, p = 0.044) and chronic kidney disease (hazard ratio [HR]: 8.730, 95% CI: 2.175–35.036, p = 0.002).

Conclusions

The heterogeneous neointima in DES-treated lesions was associated with a higher incidence of non-TLR and target lesion failure. This finding suggests that the neointimal pattern may reflect the progression of the native lesion.
Evaluation of Hsp90 and mTOR inhibitors as potential drugs for the treatment of TSC1/TSC2 deficient cancer
Authors: Mrozek Evelyn M. , Bajaj Vineeta , Guo Yanan , Malinowska Izabela A. , Zhang Jianming , Kwiatkowski David J.
Published: April 2021

Inactivating mutations in either TSC1 or TSC2 cause Tuberous Sclerosis Complex, an autosomal dominant disorder, characterized by multi-system tumor and hamartoma development. Mutation and loss of function of TSC1 and/or TSC2 also occur in a variety of sporadic cancers, and rapamycin and related drugs show highly variable treatment benefit in patients with such cancers. The TSC1 and TSC2 proteins function in a complex that inhibits mTORC1, a key regulator of cell growth, which acts to enhance anabolic biosynthetic pathways. In this study, we identified and validated five cancer cell lines with TSC1 or TSC2 mutations and performed a kinase inhibitor drug screen with 197 compounds. The five cell lines were sensitive to several mTOR inhibitors, and cell cycle kinase and HSP90 kinase inhibitors. The IC50 for Torin1 and INK128, both mTOR kinase inhibitors, was significantly increased in three TSC2 null cell lines in which TSC2 expression was restored. Rapamycin was significantly more effective than either INK128 or ganetespib (an HSP90 inhibitor) in reducing the growth of TSC2 null SNU-398 cells in a xenograft model. Combination ganetespib-rapamycin showed no significant enhancement of growth suppression over rapamycin. Hence, although HSP90 inhibitors show strong inhibition of TSC1/TSC2 null cell line growth in vitro, ganetespib showed little benefit at standard dosage in vivo. In contrast, rapamycin which showed very modest growth inhibition in vitro was the best agent for in vivo treatment, but did not cause tumor regression, only growth delay.
Awareness regarding risk factors and determinants of cancers among Bahir Dar city residents, Northwest Ethiopia
Authors: Bantie Getasew Mulat , Aynie Amare Alamirew , Gelaw Yared Mulu , Kasa Ayele Semachew , Alemayehu Meron Asmamaw , Tamirat Koku Sisay , Tsegaye Gebiyaw Wudie , Wassie Gizachew Tadesse , Kassa Tigabu Birhan , Dessie Amanuel Addisu
Published: April 2021

Background

Cancer is the second leading cause of death in the world. Knowing the cancer risk factors could help the policy-makers to design appropriate preventive and control strategies.

Objective

To investigate the awareness regarding risk factors and determinants of cancers among Bahir Dar city residents, northwest, 2019

Methods

A community-based cross-sectional study was employed. A systematic random sampling technique was carried out to select 845 study participants from May 1 to June 30, 2019. A validated structured cancer awareness measuring tool was used to collect the data. The data were entered into the Epi-data version 3.1 and analyzed using SPSS version 21 software. A simple logistic regression was run, and AOR (adjusted odds ratio) at a 95% confidence interval was used to identify the determinants of awareness regarding risk factors of cancers.

Results

Nearly twenty percent of the respondents had a good awareness regarding risk factors of cancers. An orthodox Christian (AOR = 3. 2; 95%CI: 1.8, 5.6), college graduated (AOR = 2. 3; 95%CI:1.1, 4.9), a family member with cancer (AOR = 2. 0; 95%CI: 1.3, 3.3), and living in a rental house (AOR = 0. 6; 95%CI: 0.4, 0.9) were significantly associated with awareness regarding risk factors of cancers.

Conclusion

The study revealed that awareness regarding risk factors of cancers was very low in the study area. Being Orthodox Christian, college graduated, a family member with cancer, and living in the rental house were the determinants of awareness regarding risk factors of cancers.
Activation of platelet-rich plasma by pulse electric fields: Voltage, pulse width and calcium concentration can be used to control and tune the release of growth factors, serotonin and hemoglobin
Authors: Neculaes Bogdan , Frelinger Andrew L. , Gerrits Anja J. , Gremmel Thomas , Forde Emma E. , Klopman Steven , Carmichael Sabrina L. , Michelson Alan D.
Published: April 2021

Activated platelet-rich plasma (PRP) has been used in the clinical settings of wound healing and regenerative medicine, with activation typically induced by the addition of bovine thrombin. To eliminate issues with availability, cost and potential side effects associated with bovine thrombin, ex vivo PRP activation using pulse electric fields (PEF) has been proposed and demonstrated. The present study characterizes the effect of PEF voltage and pulse width, in combination with a range of calcium concentrations, on clot formation, growth factor release, and serotonin (5-HT) release from dense granules. The main findings are: 1) increasing calcium concentrations with most PEF conditions leads to increased levels of PDGF and 5-HT release; 2) whether EGF levels increase or decrease with increasing calcium concentration depends on the specific PEF parameters; 3) the pattern of PDGF and EGF levels in supernatants suggest that these molecules are localized differently within platelets; 4) significant levels of PDGF, EGF, and 5-HT can be released without inducing clot formation or hemoglobin release. In conclusion, voltage, pulse width and calcium concentration can be used to control and tune the release of growth factors, serotonin and hemoglobin from PEF-activated PRP. Because growth factor requirements vary for different types of wounds and for wounds at different stages of healing, the unique balance of factors in supernatants of PEF-activated PRP may provide more clinically advantageous than the current standard of bovine thrombin-activated PRP.
Survival analysis of patients with tuberculosis and risk factors for multidrug-resistant tuberculosis in Monrovia, Liberia
Authors: Carter Boye Bobby , Zhang Yang , Zou Hangjin , Zhang Chuhan , Zhang Xinming , Sheng Rongtian , Qi Yanfei , Kou Changgui , Li Yin
Published: April 2021

We reviewed the records of 337 confirmed cases of tuberculosis patients in Monrovia, the capital of Liberia, 2015. The risk factors affecting the survival and multidrug-resistance of tuberculosis patients were examined. Kaplan-Meier analysis and the log-rank test were used to assess the differences in survival among the patients, while Cox regression model was used for multivariate analysis. The qualitative data was tested with chi-square test in the single factor analysis of multidrug-resistant TB. Multivariate analysis was performed using binary logistic regression analysis. The significance level for all the tests were set at 0.05. The mean period of the follow-up of patients was 10 months. In the 337 patients, 33 (9.8%) died, the 21-month survival rate was 90.2%. The results of multivariate Cox regression analysis show that overcrowding (HR = 7.942, 95% CI 3.258–19.356), former smoking (HR = 3.773, 95% CI 1.601–8.889), current smoking (HR = 3.546, 95% CI 1.195–10.521), multidrug-resistance tuberculosis (HR = 4.632, 95% CI 1.913–11.217) were risk factors for death during anti-tuberculosis treatment in TB patients in Liberia. The results of binary logistic regression analysis show that extra-pulmonary (OR = 2.032, 95% CI 1.133–3.644), family history of TB (OR = 2.387, 95% CI 1.186–4.807) and current smoking (OR = 3.436, 95% CI 1.681–7.027) were risk factors for multidrug-resistant tuberculosis. These results can provide insights on local tuberculosis early intervention, increase public health awareness, and strengthen the control of factors that may affect the survival and multidrug-resistance of tuberculosis patients.
Comparative metabolomics studies of blood collected in streck and heparin tubes from lung cancer patients
Authors: Goldberg Erin , Ievari-Shariati Shiva , Kidane Biniam , Kim Julian , Banerji Shantanu , Qing Gefei , Srinathan Sadeesh , Murphy Leigh , Aliani Michel
Published: April 2021

Metabolomics analysis of blood from patients (n = 42) undergoing surgery for suspected lung cancer was performed in this study. Venous and arterial blood was collected in both Streck and Heparin tubes. A total of 96 metabolites were detected, affected by sex (n = 56), collection tube (n = 33), and blood location (n = 8). These metabolites belonged to a wide array of compound classes including lipids, acids, pharmaceutical agents, signalling molecules, vitamins, among others. Phospholipids and carboxylic acids accounted for 28% of all detected compounds. Out of the 33 compounds significantly affected by collection tube, 18 compounds were higher in the Streck tubes, including allantoin and ketoleucine, and 15 were higher in the Heparin tubes, including LysoPC(P-16:0), PS 40:6, and chenodeoxycholic acid glycine conjugate. Based on our results, it is recommended that replicate blood samples from each patient should be collected in different types of blood collection tubes for a broader range of the metabolome. Several metabolites were found at higher concentrations in cancer patients such as lactic acid in Squamous Cell Carcinoma, and lysoPCs in Adenocarcinoma and Acinar Cell Carcinoma, which may be used to detect early onset and/or to monitor the progress of the cancer patients.
Elucidating the effect of biofertilizers on bacterial diversity in maize rhizosphere soil
Authors: Wang Junhong , Liu Lei , Gao Xiaoyin , Hao Jianxia , Wang Mengliang
Published: April 2021

This study was conducted to investigate the effect of biofertilizers on the structure and diversity of the rhizosphere bacterial community of maize. Different biofertilizers were applied to maize. The physical and chemical properties of rhizosphere soil samples were analyzed and the rhizosphere bacteria were analyzed by 16S amplicon sequencing. The results showed that treatment with Bacillus licheniformis and B. amyloliquefaciens as biofertilizers increased the soil organic matter (SOM), total nitrogen, total phosphorus (TP), available phosphorus (AP), and available potassium (AK) contents, indicating that the plant growth-promoting rhizobacteria in the biofertilizers might help the host plant to produce root exudates that, in return, recruit beneficial communities due to available sugars, amino acids, organic acids, vitamins, and polymers. The rhizosphere of maize treated with B. subtilis biofertilizer had the highest diversity and richness. However, the rhizosphere treated with the combined bacterial strains had the lowest diversity and richness, which might be due to the directional increase of the abundance of some bacteria with special functions, but the decrease of the overall bacterial community diversity in the soil. The dominant bacterial phyla were Proteobacteria (32.2%–34.6%), Acidobacteria (15.0%–21.0%), Actinobacteria (13.1%–17.2%), and Gemmatimonadetes (9.0%–10.8%), and the dominant bacterial species were Aciditerrimonas ferrireducens JCM 15389 (4.3%–5.2%), Gemmatimonas aurantiaca (3.2%–4.1%), and Pyrinomonas methylaliphatogenes (2.1%–4.8%). The significantly enriched bacterial functions were associated with amino acid metabolism, sugar metabolism, and energy metabolism pathways. The results of a redundancy analysis showed that SOM, TP, and AK were the main factors affecting the microbial community structure in the maize rhizosphere. In conclusion, the application of biofertilizers increased the diversity and richness of the bacterial community in the maize rhizosphere soil. However, combined strain treatment was failed and not an ideal strategy due to the lowest abundance and diversity.
Recombinant apoptosis inhibitor of macrophage protein reduces delayed graft function in a murine model of kidney transplantation
Authors: Lee Ji Yun , Arumugarajah Shabitha , Lian Dameng , Maehara Natsumi , Haig Aaron R. , Suri Rita S. , Miyazaki Toru , Gunaratnam Lakshman
Published: April 2021

Reperfusion injury following cold and warm ischemia (IRI) is unavoidable during kidney transplantation and contributes to delayed graft function (DGF) and premature graft loss. Death of tubular epithelial cells (TECs) by necrosis during IRI releases pro-inflammatory mediators (e.g. HMGB1), propagating further inflammation (necroinflammation) and tissue damage. Kidney Injury Molecule-1 (KIM-1) is a phagocytic receptor upregulated on proximal TECs during acute kidney injury. We have previously shown that renal KIM-1 protects the graft against transplant associated IRI by enabling TECs to clear apoptotic and necrotic cells, and that recognition of necrotic cells by KIM-1 is augmented in the presence of the opsonin, apoptosis inhibitor of macrophages (AIM). Here, we tested whether recombinant AIM (rAIM) could be used to mitigate transplant associated IRI. We administered rAIM or vehicle control to nephrectomised B6 mice transplanted with a single B6 donor kidney. Compared to grafts in vehicle-treated recipients, grafts from rAIM-treated mice exhibited significantly less renal dysfunction, tubular cell death, tissue damage, tubular obstruction, as well as local and systemic inflammation. Both mouse and human rAIM enhanced the clearance of necrotic cells by murine and human TECs, respectively in vitro. These data support testing of rAIM as a potential therapeutic agent to reduce DGF following kidney transplantation.