bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanofat Cell Aggregates: A Nearly Constitutive Stromal Cell Inoculum for Regenerative Site-Specific Therapies
Authors: Sesé Borja , Sanmartín Javier M. , Ortega Bernat , Matas-Palau Aina , Llull Ramon 
Published: August 2019

Background:
Recent technology developed by Tulip Medical Products allows clinicians to mechanically disaggregate fat tissue into small fat particles known as nanofat. The present study aimed to evaluate the cell yield obtained from nanofat generation in comparison to traditional methods involving enzymatic dissociation (stromal vascular fraction).

Methods:
Nanofat preparations were characterized by cell content and viability, based on DNA quantification and image cytometry, respectively. DNA analysis was also used to determine the cell content in unprocessed dry lipoaspirate and native adipose tissue (excised adipose tissue). To evaluate cell yield, the authors compared the number of cells recovered from 1 g of lipoaspirate between stromal vascular fraction and nanofat preparations, and subsequently determined the final cell inoculum obtained following their respective protocols.

Results:
The data showed that nanofat samples presented a cell burden of 7.3 million cells/g, close to 80 percent of unprocessed dry lipoaspirate, and 70 percent of native excised adipose tissue. Moreover, cell viability was not altered by mechanical disaggregation in nanofat samples compared to unprocessed dry lipoaspirate. Nanofat samples exhibited a cell yield of 6.63 million cells/g lipoaspirate, whereas stromal vascular fraction preparations resulted in only 0.68 million cells/g lipoaspirate. The final cell inoculum obtained from stromal vascular fraction isolation was 120 million cells and it required 200 to 250 cc of raw lipoaspirate as starting material, whereas nanofat preparation resulted in 125 million cells with only 20 cc of raw lipoaspirate.

Conclusion:
Mechanical disaggregation offers a better cell inoculum than conventional enzymatic dissociation methods by using 10 times less fat tissue as starting material and delivering a higher cell yield.
Lean-Oriented Layout Design of a Health Care Facility
Authors: Fogliatto Flavio S. , Tortorella Guilherme L. , Anzanello Michel J. , Tonetto Leandro M. 
Published: August 2019

Background:
In this article, we propose a method that integrates systematic layout planning techniques to lean health care practices aided by multicriteria decision analysis that could be applied to reformulate the layout of health care facilities.

Methods:
We analyze a high-variety sterilization unit of a large public hospital located in Brazil. The unit is currently implementing lean practices, and layout changes are required to provide more efficient materials and information flows.

Results:
Traditional design of health care facilities is not aligned with lean implementation and its underlying practices and principles. We propose the integration of such approaches to enhance their benefits. To rank and select the best layout alternative, a multicriteria decision analysis method (analytic hierarchy process) is adopted.

Conclusions:
There are 3 contributions here: the integration of lean principles into traditional health care facility design practices, the use of multicriteria decision analysis to refine the determination of the best layout solution, and the application of our propositions in a real case study.
A Rapid Cycle Improvement Approach to Increase Patient Readiness at Their Scheduled Appointment Time
Authors: Cowdell Jed Colt , Smoot Teresa B. , Murray Loren P. , Stancampiano Fernando F. , Hedges Mary S. 
Published: August 2019

Background:
Patient unpunctuality negatively affects quality care. We found that 39% of patients at an academic primary care center were not ready to be evaluated at their scheduled appointment time. Our aim was to reduce this to 20% in 3 months' time.

Intervention:
A multidisciplinary quality improvement team utilized quality improvement tools and methodology to determine that patient punctuality was a major modifiable factor contributing to the care gap. Reforming the scheduling process to include a built in 15-minute early arrival was implemented for acute visits for a 2-week trial period. Based on the successful results, this was then disseminated to all appointment types for a 3-month trial.

Results:
Of the 182 patients seen during the 2-week trial period, 34 (19%) were not ready to be seen at the time of their appointment, a 20% improvement (P value < .001) from baseline. A total of 2832 patients were followed up for all visits during the next 3 months and 590 (21%) were not ready on time (P value < .001). Physician and patient satisfaction results improved after the intervention.

Conclusions:
Utilizing quality improvement tools we were able to find a simple and inexpensive intervention to improve patient punctuality as well as patient and provider satisfaction.
Patient Involvement in Evaluation of Safety in Oral Antineoplastic Treatment: A Failure Mode and Effects Analysis in Patients and Health Care Professionals
Authors: Mattsson Thea Otto , Lipczak Henriette , Pottegård Anton 
Published: August 2019

Objectives:
To identify risks associated with delivery of treatment with oral antineoplastic agents in an outpatient setting and to evaluate additional value and feasibility of engaging patients in a proactive risk analysis.

Methods:
We conducted 2 separate but parallel failure mode and effects analyses (FMEAs) among patients and health care professionals (HCPs) at a clinical oncology department in Denmark. Comparative analyses were performed using the FMEA process maps and risk priority numbers (RPNs) as main outcome measures. The FMEAs were augmented by semistructured interviews with HCPs and patients on acceptability and feasibility of FMEAs analyzed using systematic text condensation.

Results:
Patients and HCPs found failures in information regarding treatment (cause, aim, and plan) to be of high risk. Also, HCPs found failures in checking for potential interactions to be of high risk. HCPs focused on the in-hospitals procedures, whereas patients identified risks related to both the hospital and the home setting. Both HCPs and patients found participation in the FMEA process meaningful but found the use of RPNs difficult.

Conclusions:
Patient engagement in proactive risk analysis using FMEA is acceptable, meaningful, and feasible, with patients providing a different perspective on the risks associated with oral antineoplastic treatment compared with HCPs.
Alternative Complement Pathway Activation Provokes a Hypercoagulable State with Diminished Fibrinolysis
Authors: Samuels Jason M. , Coleman Julia R. , Moore Ernest E. , Bartley Matt , Vigneshwar Navin , Cohen Mitchell , Silliman Christopher C. , Sauaia Angela , Banerjee Anirban 
Published: August 2019

ABSTRACT

Introduction:
Several disease processes trigger prolonged activation of the alternative complement pathway. Crosslinks between complement activation and physiologic changes in platelets and neutrophils have been identified, but how this interplay alters the hemostatic potential in humans remains undefined. We hypothesize that activation of the alternative pathway triggers a hypercoagulable state.

Methods:
C3/C5 convertase Cobra Venom Factor (CVF, 10 Units/mL) was employed to activate the alternative complement pathway in whole blood. Complement inhibition was completed with inhibitors for C3/C3b (Compstatin, 25 and 50 μM), C3a receptor (SB290157, 300 nM, C3aR), and C5a receptor (W54011, 6 nM, C5aR). Coagulation was assessed using native thrombelastography which produces the following: reaction time (R time); angle; maximum amplitude (MA); percent fibrinolysis at 30-min post-MA (LY30).

Results:
Inhibition with C3aR and C5aR inhibitors did not alter clot formation (R time, 11.2 vs 11.6 min, P = 0.36), clot strength (MA, 52.0 vs 52.3 mm, P = 0.43), or fibrinolysis (LY30, 1.6 vs 4.0%, P = 0.19). Compstatin did not influence clot formation or clot strength but did induce a dose-dependent increase in fibrinolysis (control LY30 3.0 vs 7.8% and 12.4% for 25 and 50 μM respectively, P = 0.0002). CVF increased MA (58.0 vs 62.8 mm, P < 0.0001), decreased LY30 (2.3 vs 1.4%, P = 0.004), and increased R time (8.4 vs 9.9 min, P = 0.008). Compstatin reversed the effects of CVF, while C5a reversed only the change in LY30.

Conclusions:
C3 contributes to fibrinolysis, as inhibition with Compstatin enhanced fibrinolysis, and CVF cleavage of C3 decreased fibrinolysis. CVF also induced a hypercoagulable state with increased clot strength.
Complete metamorphosis of insects
Authors: Rolff Jens , Johnston Paul R. , Reynolds Stuart 
Published: August 2019

The majority of described hexapod species are holometabolous insects, undergoing an extreme form of metamorphosis with an intercalated pupal stage between the larva and adult, in which organs and tissues are extensively remodelled and in some cases completely rebuilt. Here, we review how and why this developmental strategy has evolved. While there are many theories explaining the evolution of metamorphosis, many of which fit under the hypothesis of decoupling of life stages, there are few clear adaptive hypotheses on why complete metamorphosis evolved. We propose that the main adaptive benefit of complete metamorphosis is decoupling between growth and differentiation. This facilitates the exploitation of ephemeral resources and enhances the probability of the metamorphic transition escaping developmental size thresholds. The evolution of complete metamorphosis comes at the cost of exposure to predators, parasites and pathogens during pupal life and requires specific adaptations of the immune system at this time. Moreover, metamorphosis poses a challenge for the maintenance of symbionts and the gut microbiota, although it may also offer the benefit of allowing an extensive change in microbiota between the larval and adult stages. The regulation of metamorphosis by two main players, ecdysone and juvenile hormone, and the related signalling cascades are now relatively well understood. The mechanics of metamorphosis have recently been studied in detail because of the advent of micro-CT and research into the role of cell death in remodelling tissues and organs. We support the argument that the adult stage must necessarily have preceded the larval form of the insect. We do not resolve the still contentious question of whether the larva of insects in general originated through the modification of existing preadult forms or through heterochrony as a modified embryonic stage (pronymph), nor whether the holometabolous pupa arose as a modified hemimetabolous final stage larva.This article is part of the theme issue ‘The evolution of complete metamorphosis’.
The evolution of insect metamorphosis: a developmental and endocrine view
Authors: Truman James W. , Riddiford Lynn M. 
Published: August 2019

Developmental, genetic and endocrine data from diverse taxa provide insight into the evolution of insect metamorphosis. We equate the larva–pupa–adult of the Holometabola to the pronymph–nymph–adult of hemimetabolous insects. The hemimetabolous pronymph is a cryptic embryonic stage with unique endocrinology and behavioural modifications that probably served as preadaptations for the larva. It develops in the absence of juvenile hormone (JH) as embryonic primordia undergo patterning and morphogenesis, the processes that were arrested for the evolution of the larva. Embryonic JH then drives tissue differentiation and nymph formation. Experimental treatment of pronymphs with JH terminates patterning and induces differentiation, mimicking the processes that occurred during the evolution of the larva. Unpatterned portions of primordia persist in the larva, becoming imaginal discs that form pupal and adult structures. Key transcription factors are associated with the holometabolous life stages:Krüppel-homolog 1(Kr-h1) in the larva,broadin the pupa andE93in the adult. Kr-h1 mediates JH action and is found whenever JH acts, while the other two genes direct the formation of their corresponding stages. In hemimetabolous forms, the pronymph has low Broad expression, followed by Broad expression through the nymphal moults, then a switch to E93 to form the adult.This article is part of the theme issue ‘The evolution of complete metamorphosis’.
Evaluating responses to temperature during pre-metamorphosis and carry-over effects at post-metamorphosis in the wood tiger moth (Arctia plantaginis)
Authors: Galarza Juan A. , Dhaygude Kishor , Ghaedi Behnaz , Suisto Kaisa , Valkonen Janne , Mappes Johanna 
Published: August 2019

Insect metamorphosis is one of the most recognized processes delimiting transitions between phenotypes. It has been traditionally postulated as an adaptive process decoupling traits between life stages, allowing evolutionary independence of pre- and post-metamorphic phenotypes. However, the degree of autonomy between these life stages varies depending on the species and has not been studied in detail over multiple traits simultaneously. Here, we reared full-sib larvae of the warningly coloured wood tiger moth (Arctia plantaginis) in different temperatures and examined their responses for phenotypic (melanization change, number of moults), gene expression (RNA-seq and qPCR of candidate genes for melanization and flight performance) and life-histories traits (pupal weight, and larval and pupal ages). In the emerging adults, we examined their phenotypes (melanization and size) and compared them at three condition proxies: heat absorption (ability to engage flight), flight metabolism (ability to sustain flight) and overall flight performance. We found that some larval responses, as evidenced by gene expression and change in melanization, did not have an effect on the adult (i.e. size and wing melanization), whereas other adult traits such as heat absorption, body melanization and flight performance were found to be impacted by rearing temperature. Adults reared at high temperature showed higher resting metabolic rate, lower body melanization, faster heating rate, lower body temperature at take-off and inferior flight performance than cold-reared adults. Thus, our results did not unambiguously support the environment-matching hypothesis. Our results illustrate the importance of assessing multiple traits across life stages as these may only be partly decoupled by metamorphosis.This article is part of the theme issue ‘The evolution of complete metamorphosis'.
A flexible quantitative phase imaging microscope for label-free imaging of thick biological specimens using aperture masks
Authors: Seniya Chandrabhan , Towers Catherine E , Towers David P 
Published: August 2019

AbstractA flexible quantitative phase imaging microscope is reported that offers new capabilities in terms of phase measurement from both thin and thick biological specimens. The method utilises Zernike’s phase contrast approach for label-free imaging with a Twymann-Green based phase shifting module in the back focal plane. The interfering wave fronts are manipulated by laser cut apertures to form the scattered and non-scattered fields. The design is flexible and low-cost. It is shown that the bandwidth of the optical source can be optimised to enable larger optical path differences to be measured whilst giving essentially speckle free imaging. Phase maps of the cell membrane, nucleus and nucleolus of transparent epidermis cells of Allium cepa have been examined as proof of concept. Measurements from a range of glass beads confirm the optical path difference capability. The implementation of the phase shifting module is < 10% of the cost of that using a spatial light modulator whilst delivering equivalent phase resolution.
Multiple Myeloma DREAM Challenge Reveals Epigenetic RegulatorPHF19As Marker of Aggressive Disease
Authors: Mason Mike J , Schinke Carolina , Eng Christine L P , Towfic Fadi , Gruber Fred , Dervan Andrew , White Brian S , Pratapa Aditya , Guan Yuanfang , Chen Hongjie , Cui Yi , Li Bailiang , Yu Thomas , Neto Elias Chaibub , Mavrommatis Konstantinos , Ortiz Maria , Lyzogubov Valeriy , Bisht Kamlesh , Dai Hongyue Y , Schmitz Frank , Flynt Erin , Rozelle Dan , Danziger Samuel A , Ratushny Alexander ,   Multiple Myeloma DREAM Consortium, Dalton William S , Goldschmidt Hartmut , Avet-Loiseau Herve , Samur Mehmet , Hayete Boris , Sonneveld Pieter , Shain Kenneth H , Munshi Nikhil , Auclair Daniel , Hose Dirk , Morgan Gareth , Trotter Matthew , Bassett Douglas , Goke Jonathan , Walker Brian A , Thakurta Anjan , Guinney Justin 
Published: August 2019

AbstractWhile the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients do not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involve assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post challenge analysis identified a novel expression-based risk marker and histone modifier,PHF19, which featured prominently in several independent models. Lastly, we show that a simple four feature predictor composed of age, International Staging System stage (ISS), and expression ofPHF19andMMSETperforms similarly to more complex models with many more gene expression features included.Key pointsMost comprehensive and unbiased assessment of prognostic biomarkers in MM resulting in a robust and parsimonious model.Identification ofPHF19as the expression based biomarker most strongly associated with rapid progression in MM patients.
Structural-stability studies on recombinant human transferrin
Authors: Kulakova A. , Indrakumar S. , Sønderby P. , Gentiluomo L. , Streicher W. , Roessner D. , Frieß W. , Peters G. H.J. , Harris P. 
Published: August 2019

AbstractTransferrin is an attractive candidate for drug delivery due to its ability to cross the blood brain barrier. However, in order to be able to use it for therapeutic purposes, it is important to investigate how its stability depends on different formulation conditions. Combining high-throughput thermal and chemical denaturation studies with small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, it was possible to connect the stability of transferrin with its conformational changes. The release of iron induces opening of transferrin, which results in a negative effect on its stability. Presence of NaCl, arginine, and histidine leads to opening of the transferrin N-lobe and has a negative impact on the overall protein stability.Statement of significanceProtein-based therapeutics have become an essential part of medical treatment. They are highly specific, have high affinity and fewer off-target effects. However, stabilization of proteins is critical, time-consuming, and expensive, and it is not yet possible to predict the behavior of proteins under different conditions. The current work is focused on a molecular understanding of the stability ofhumanserum transferrin; a protein which is abundant in blood serum, may pass the blood brain barrier and therefore with high potential in drug delivery. Combination of high throughput unfolding techniques and structural studies, using small angle X-ray scattering and molecular dynamic simulation, allows us to understand the behavior of transferrin on a molecular level.
Population genomics of Vibrionaceae isolated from an endangered oasis reveals local adaptation after an environmental perturbation
Authors: Vazquez-Rosas-Landa Mirna , Ponce-Soto Gabriel Yaxal , Aguirre-Liguori Jonás A. , Thakur Shalabh , Scheinvar Enrique , Barrera-Redondo Josué , Ibarra-Laclette Enrique , Guttman David S. , Eguiarte Luis E. , Souza Valeria 
Published: August 2019

BackgroundIn bacteria, pan-genomes are the result of the evolutionary “tug of war” between selection and horizontal gene transfer (HGT). High rates of HGT increase the genetic pool and the effective population size, resulting in open pan-genomes. In contrast, selective pressures can lead to local adaptation by purging the variation introduced by HGT, resulting in closed pan-genomes and clonal lineages. In this study, we explored both hypotheses elucidating the pan-genome of Vibrionaceae isolates after a perturbation event in the endangered oasis of Cuatro Ciénegas Basin (CCB), Mexico, and looking for signals of adaptation to the environments in their genomes.ResultsWe obtained 42 genomes of Vibrionaceae distributed in six lineages, two of them did not showed any close reference strain in databases. Five of the lineages showed closed pan-genomes and were associated to either water or sediment environment; their high effective population size (Ne) estimates suggest that these lineages are not from a recent origin. The only clade with an open pan-genome was found in both environments and was formed by ten genetic groups with lowNe, suggesting a recent origin. The recombination and mutation estimators (r/m) ranged from 0.0052 to 2.7249, which are similar to oceanic Vibrionaceae estimations; however, we identified 367 gene families with signals of positive selection, most of them found in the core genome; suggesting that despite recombination, natural selection moves the Vibrionaceae CCB lineages to local adaptation purging the genomes and keeping closed pan-genome patterns. Moreover, we identify 598 SNPs associated with an unstructured environment; some of the genes under this SNPs were related to sodium transport.ConclusionsDifferent lines of evidence suggest that the sampled Vibrionaceae, are part of the rare biosphere usually living under famine conditions. Two of these lineages were reported by the first time. Most Vibrionaceae lineages of CCB are adapted to their microhabitats rather than to the sampled environments. This pattern of adaptation agrees with the association of closed pan-genomes and local adaptation.
A 3D High Resolution Generative Deep-learning Network for Fluorescence Microscopy Image
Authors: Hang Zhou , Shiwei Li , Qing Huang , Shijie Liu , Tingwei Quan , Cai Ruiyao , Ertürk Ali , Shaoqun Zeng 
Published: August 2019

AbstractDeep learning technology enables us acquire high resolution image from low resolution image in biological imaging free from sophisticated optical hardware. However, current methods require a huge number of the precisely registered low-resolution (LR) and high-resolution (HR) volume image pairs. This requirement is challengeable for biological volume imaging. Here, we proposed 3D deep learning network based on dual generative adversarial network (dual-GAN) framework for recovering HR volume images from LR volume images. Our network avoids learning the direct mappings from the LR and HR volume image pairs, which need precisely image registration process. And the cycle consistent network makes the predicted HR volume image faithful to its corresponding LR volume image. The proposed method achieves the recovery of 20x/1.0 NA volume images from 5x/0.16 NA volume images collected by light-sheet microscopy. In essence our method is suitable for the other imaging modalities.