bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of synthetic microRNA‐214 showing enhanced cytotoxicity and RNase resistance for treatment of canine hemangiosarcoma
Authors: Yoshikawa Ryutaro , Heishima Kazuki , Ueno Yoshihito , Kawade Miwa , Maeda Yusuke , Yoshida Kyoko , Murakami Mami , Sakai Hiroki , Akao Yukihiro , Mori Takashi 
Published: February 2020

AbstractMicroRNA‐214 (miR‐214), a pivotal tumour‐suppressive miRNA, is downregulated in canine hemangiosarcoma (HSA) cells. Although these tumour‐suppressive miRNAs are potential therapeutic agents, their clinical efficacy may be limited because of their vulnerability to RNase‐rich microenvironments and low in vivo transfection rates. We developed synthetic miR‐214s with enhanced cytotoxicity, RNase resistance and quantity of miR‐214 in/on cells. These synthetic miR‐214s were synthesized by various chemical modifications (such as 4′‐aminoethyl‐2′‐fluoro, 2′‐fluoro, 2′‐O‐methyl, phosphorothioate and oligospermine modifications) of the wild‐type mature miR‐214 sequences. Transfection of HSA cells with synthetic miR‐214 (miR‐214 5AE) demonstrated significant growth suppressive effect and induced the strongest apoptotic response. Synthetic miR‐214s (miR‐214 5AE, miR‐214 10AE and miR‐214 OS) were much more stable than mature miR‐214s in foetal bovine serum. Similar to mature miR‐214, 5AE and OS suppressed the expression level of COP1 in HSA cells. The quantity of synthetic miR‐214s in/on cells was higher than that of mature miR‐214. In conclusion, we developed a clinically applicable, synthetic miR‐214 5AE that regulates the COP1 protein expression similar to that mediated by mature miR‐214. Additionally, miR‐214 5AE confers better cytotoxicity, nuclease resistance and transfection rate than mature miR‐214. Thus, miR‐214 5AE could potentially be a novel miRNA‐based chemotherapeutic agent that could improve the prognosis of HSA. Its in vivo effects on canine HSA need to be examined in future.
Ultrafast fiber laser delivering conservative, dispersion-managed, and dissipative solitons
Authors: Park N. 
Published: February 2020

A thulium-doped fiber laser, delivering the temporal solitons, has been proposed with a carbon nanotubes saturable absorber. By adjusting the dispersion design in the laser cavity, the proposed laser can generate three types of solitons, which are conservative soliton (CS), dispersion-managed soliton (DMS), and dissipative soliton (DS), respectively. The experimental results show that, for the first time to the best of our knowledge, the autocorrelation traces of CS, DMS, and DS are in good agreement with hyperbolic secant curve, Gaussian curve, and super-Gaussian curve, respectively. DS with the broad spectral bandwidth of 45.3 nm is emitted from the cavity while the dispersion is adjusted to 0.005 ps2.
Squares and associative representations of two-dimensional evolution algebras
Authors: Cardoso Gonçalves Maria Inez , Gonçalves Daniel , Barquero Dolores Martín , González Cándido Martín , Molina Mercedes Siles 
Published: February 2020

We associate a square to any two-dimensional evolution algebra. This geometric object is uniquely determined, does not depend on the basis and describes the structure and the behavior of the algebra. We determine the identities of degrees at most four, as well as derivations and automorphisms. We look at the group of automorphisms as an algebraic group, getting in this form a new algebraic invariant. The study of associative representations of evolution algebras is also started and we get faithful representations for most two-dimensional evolution algebras. In some cases, we prove that faithful commutative and associative representations do not exist, giving rise to the class of what could be termed as “exceptional” evolution algebras (in the sense of not admitting a monomorphism to an associative algebra with deformed product).
Computer simulation of shearing deformation in polymer systems with polar groups
Authors: Maksimova Olga G. , Piskunov Oleg S. , Gerasimov Roman A. , Baruzdina Olga S. , Maksimov Andrew V. 
Published: February 2020

In this work, shear strain modeling in materials consisting of a thin polymer layer ([Formula: see text][Formula: see text]nm), adhesive bonded to a rigid substrate, considered not to be impacted by deformation, was performed. A discrete-continuum model of chains system with a given stiffness with polar groups is developed. The polymer chain was considered in the framework of the persistene model, and the polar groups were based on the lattice model on the tetragonal lattice. It was assumed that the main contribution to the energy of interchain interactions is due to the potential of the polar groups and was calculated using the Metropolis algorithm. The potential interactions between the nearest polar groups of chains included the energy of dipole–dipole interactions (Keesom energy) and the Lennard–Jones potential. It is taken into account that the possible orientations of the polar groups are determined by the average elongation of the chain. Calculations showed that the dependence of free energy on the interchain distance has two minima. The first minimum is characterized by the orientational ordering of the polar groups, the second — by their disordered state. The depth and position of the minima depend on temperature, bending stiffness of the chain, the modulus of the dipole moment of the polar groups and the depth of the potential well in the Lennard–Jones energy. A step-by-step simulation of shear strain in a polymer layer in an orientationally disordered state was carried out. The obtained stress–strain diagrams make it possible to estimate the value of the elastic limit and also to determine the stresses at the points of phase transitions from a disordered to an orientationally ordered state.
Inmates as Labour Pool: A Case of Inter-organizational Collaboration
Authors: Shree Sonal , Brahmankar Yogesh , Singh Ardhendu Shekhar 
Published: February 2020

Businesses grapple with mounting costs of accessing labour pools for recruitment. At the same time, the jail administrations struggle to find recruiters for a skilled group of convicts. Can collaboration help? It is in this light that the case focusses on the prison system in India and the provision of training and employment within the jail premises. The jail industries serve the dual role of production and training units for convicts and equip them with the necessary skills to help them earn wages as their source of livelihood for the present as well as to secure their future. Inter-organizational collaboration in this case has the potential to provide the much-needed impetus by offering a much larger number of tasks required to engage all convicts. The case highlights the challenges faced by jail authorities in the absence of sufficient tasks versus the increasing number of convicts, and the dilemma and scepticism of businesses in recruiting from prisons. It also leads to the innovative and socially responsible aspect of training and recruitment in organizations through initiatives at the Yerwada and Kolhapur Central jails in Maharashtra, India. Dilemma Purposive engagement of prisoners outside the prison without any breach of security was a prime concern. An opportunity or risk, what could it turn out to be? Theory: Inter-organizational collaboration Type of the Case: Problem solving, Primary data Protagonist: DIG Sathe Options The jobs were selected based on the security needs, matching competency, low set-up and training cost and future expansions. Initially jail authorities leased out portions of premises to firms. Inventory were brought in the jail and finished items were transported back to the user. Discussions and Case Questions How to change the stereotypical portrayal of jail environment as a place to torture inmates in an effort to transform? How can firms be attracted to recruit prison inmates? Which processes will lead to reformation and rehabilitation of inmates? How can the operation be scaled up without posing a threat to security? Which measures will help in diffusing tension within a jail? Whether any inter-organizational collaboration leading to recruitment from prisons would mean an opportunity for corporate or corrective reform for inmates or a morsel of both?
The secondary KIT mutation p.Ala510Val in a cutaneous mast cell tumour carrying the activating mutation p.Asn508Ile confers resistance to masitinib in dogs
Authors: Gentilini Fabio , Turba Maria Elena , Dally Claire , Takanosu Masamine , Kurita Sena , Bonkobara Makoto 
Published: February 2020

Abstract
Background
Gain-of-function mutations in KIT are driver events of oncogenesis in mast cell tumours (MCTs) affecting companion animals. Somatic mutations of KIT determine the constitutive activation of the tyrosine kinase receptor leading to a worse prognosis and a shorter survival time than MCTs harbouring wild-type KIT. However, canine MCTs carrying KIT somatic mutations generally respond well to tyrosine kinase inhibitors; hence their presence represents a predictor of treatment effectiveness, and its detection allows implementing a stratified medical approach. Despite this, veterinary oncologists experience treatment failures, even with targeted therapies whose cause cannot be elucidated. The first case of an MCT-affected dog caused by a secondary mutation in the tyrosine kinase domain responsible for resistance has recently been reported. The knowledge of this and all the other mutations responsible for resistance would allow the effective bedside implementation of a deeply stratified and more effective medical approach.

Case presentation
The second case of a canine MCT carrying a different resistance mutation is herein described. The case was characterised by aggressive behaviour and early metastasis unresponsive to both vinblastine- and masitinib-based treatments. Molecular profiling of the tumoural masses revealed two different mutations; other than the already known activating mutation p.Asn508Ile in KIT exon 9, which is tyrosine kinase inhibitor-sensitive, a nearly adjacent secondary missense mutation, p.Ala510Val, which had never before been described, was detected. In vitro transfection experiments showed that the secondary mutation did not cause the constitutive activation by itself but played a role in conferring resistance to masitinib.

Conclusions
This study highlighted the importance of the accurate molecular profiling of an MCT in order to improve understanding of the molecular mechanism underlying tumourigenesis and reveal chemoresistance in MCTs for more effective therapies. The detection of the somatic mutations responsible for resistance should be included in the molecular screening of MCTs, and a systematic analysis of all the cases characterised by unexpected refractoriness to therapies should be investigated in depth at both the genetic and the phenotypic level.
Allergic reactions to genus Morus plants: a review
Authors: Papia F. , Incorvaia C. , Genovese L. , Gangemi S. , Minciullo P. L. 
Published: February 2020

AbstractMulberry is a plant belonging to the family Moraceae, and genus Morus. Allergic sensitization to mulberries has been reported as both food allergy or respiratory allergy, and cross-reactivity between mulberries and other pollens or fruits was described. Clinically, in the articles reporting mulberry allergy, the reactions included respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria. As far as cross-reactivity is concerned, the allergens identified thus far in mulberries include pathogenesis-related (PR)10 proteins, with sequence identity to Bet v 1 from birch, lipid transfer (LTP)1 proteins with identity with LTPs from Rosaceae family plants, panallergens groups, and also ubiquitin-like protein and cystatin-like protein. The two latter proteins account for cross-reactions with Parietaria judaica and Olea europaea. Such large cross-reactivity warrants to pay particular attention to the risk of systemic reactions to foods, particularly in subjects sensitized to birch, parietaria or olive pollens. In fact, the increasing use of mulberry as a food product, which is encouraged by its remarkable antioxidant power, expose sensitized patients to possible reactions after ingesting foods, dietary supplements or nutraceuticals containing mulberry. Mulberry allergenicity can vary according to the processing methods used since some allergens are thermostable and other loss their reactivity during heating.
Initiating renal replacement therapy through incremental haemodialysis: Protocol for a randomized multicentre clinical trial
Authors: Fernández Lucas M. , Ruíz-Roso G. , Merino J. L. , Sánchez R. , Bouarich H. , Herrero J. A. , Muriel A. , Zamora J. , Collado A. 
Published: February 2020

Abstract
Background
Thrice-weekly haemodialysis is the usual dose when starting renal replacement therapy; however, this schedule is no longer appropriate since it does not consider residual renal function. Several reports have suggested the potential benefit of beginning haemodialysis less frequently and incrementally increasing the dose as the residual renal function decreases. However, all the data published so far are from observational studies. Thus, this clinical trial avoids any potential selection bias and will assess the possible benefits that have been observed in observational studies.

Methods/design
This report describes the study protocol of a randomized prospective multi-centre open-label clinical trial to evaluate whether starting renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than the standard thrice-weekly regimen. We also explore other clinical parameters, such as concentrations of uremic toxins, dialysis doses, control of anaemia, removal of medium-weight uremic toxins, nutritional status, quality of life, hospital admissions and mortality. Only incident haemodialysis patients who can maintain a urea clearance rate KrU ≥ 2.5 mL/min/1.73 m2 are eligible. Patient recruitment began on 1 January 2017 and will last for 2 years or until the required sample size has been recruited to ensure the established statistical power has been reached. The minimum follow-up period will be 1 year. Anuric patients with acute renal failure and patients who return to haemodialysis after a kidney transplant failure are excluded. It has been calculated that 44 patients should be recruited into each group to achieve a power of 80% in a two-sided comparison of means with a usual significance level of 0.05. A time-to-event analysis will estimate the probability of kidney function survival in both groups using the Kaplan–Meier method. Survival curves will be compared with log-rank tests. This survival analysis will be complemented with a proportional hazard model to estimate the hazard ratio of kidney function survival adjusted for any confounding factors. Analyses will be carried out in accordance with the intention-to-treat principle.

Discussion
The incremental initiation of dialysis may preserve residual renal function better than the conventional treatment, with similar or higher survival rates, as reported by observational studies. To our knowledge, this is the first clinical trial to evaluate whether initiating renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than beginning with the standard thrice-weekly regimen.

Trial registration
ClinicalTrials.gov, NCT03302546. Registered on 5 October 2017.
A potential global surveillance tool for effective, low-cost sampling of invasive Aedes mosquito eggs from tyres using adhesive tape
Authors: Dallimore Thom , Goodson David , Batke Sven , Strode Clare 
Published: February 2020

AbstractBackgroundThe international movement of used tyres is a major factor responsible for global introductions ofAedesinvasive mosquitoes (AIMs) (Diptera: Culicidae) that are major disease vectors (e.g. dengue, Zika, chikungunya and yellow fever). Surveillance methods are restricted by expense, availability and efficiency to detect all life stages. Currently, no tested method exists to screen imported used tyres for eggs in diapause, the life stage most at risk from accidental introduction. Here we test the efficiency of adhesive tape as an affordable and readily available material to screen tyres for eggs, testing its effect on hatch rate, larval development, DNA amplification and structural damage on the egg surface.ResultsWe demonstrated that the properties of adhesive tape can influence pick up of dormant eggs attached to dry surfaces. Tapes with high levels of adhesion, such as duct tape, removed eggs with high levels of efficiency (97% ± 3.14). Egg numbers collected from cleaned used tyres were found to explain larval hatch rate success well, particularly in subsequent larval to adult emergence experiments. The strength of this relationship decreased when we tested dirty tyres. Damage to the exochorion was observed following scanning electron microscopy (SEM), possibly resulting in the high variance in the observed model. We found that five days was the optimal time for eggs to remain on all tested tapes for maximum return on hatch rate success. Tape type did not inhibit amplification of DNA of eggs from three, five or ten days of exposure. Using this DNA, genotyping of AIMs was possible using species-specific markers.ConclusionsWe demonstrated for the first time that adhesive tapes are effective at removing AIM eggs from tyres. We propose that this method could be a standardised tool for surveillance to provide public health authorities and researchers with an additional method to screen tyre cargo. We provide a screening protocol for this purpose. This method has a global applicability and in turn can lead to increased predictability of introductions and improve screening methods at high risk entry points.
A high capacity reversible data hiding through multi-directional gradient prediction, non-linear regression analysis and embedding selection
Authors: Hung Kuo-Ming , Yih Chi-Hsiao , Yeh Cheng-Hsiang , Chen Li-Ming 
Published: February 2020

AbstractThe technique of reversible data hiding enables an original image to be restored from a stego-image with no loss of host information, and it is known as a reversible data hiding algorithm (RDH). Our goal is to design a method to predict pixels effectively, because the more accurate the prediction is, the more concentrated the histogram is, and it minimizes shifting to avoid distortion. In this paper, we propose a new multi-directional gradient prediction method to generate more accurate prediction results. In embedding stage, according to the embedding capacity of information, we generate the best decision based on non-linear regression analysis, which can differentiate between embedding region and non-embedding region to reduce needless shifting. Finally, we utilize the automatic embedding range decision. With sorting by the amount of regional variance, the easier predicted region is prior for embedding, and the quality of the image is improved after embedding. To evaluate the proposed reversible hiding scheme, we compared other methods on different pictures. Results show that the proposed scheme can embed much more data with less distortion.
Update on KEYNOTE-199, cohorts 1-3: Pembrolizumab (pembro) for docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Antonarakis Emmanuel S. , Piulats Josep M. , Gross-Goupil Marine , Goh Jeffrey C. , Vaishampayan Ulka N. , De Wit Ronald , Alanko Tuomo , Fukasawa Satoshi , Tabata Kenichi , Feyerabend Susan , Berger Raanan , Wu Helen , Kim Jeri , Schloss Charles , De Bono Johann S. 
Published: February 2020

104 Background: The KEYNOTE-199 multicohort phase 2 study (NCT02787005) showed that pembro monotherapy has antitumor activity and acceptable safety in patients (pts) with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel in cohort 1 (C1) (RECIST-measurable, PD-L1+ disease), C2 (RECIST-measurable, PD-L1− disease), and C3 (bone-predominant disease, irrespective of PD-L1). Updated results with additional follow-up for C1-3 are presented. Methods: Pts previously received ≥1 NHAs and 1 or 2 chemotherapies, including docetaxel. Pts received pembro 200 mg Q3W for 35 cycles or until progression or intolerable toxicity. Primary end point was ORR. Key secondary end points were DCR, DOR, PSA (≥50%) response rate, rPFS, OS, and safety. Results: Of 258 pts enrolled (C1=133; C2=67; C3=58), 6 completed (C1=4; C3=2) and 252 discontinued (C1=129; C2=67; C3=56) therapy, primarily due to progression (C1=106; C2=61; C3=45). Median follow-up was 9.6 mo (C1, 9.5; C2, 7.9; C3, 14.2). ORR (95% CI) for pts with measurable disease was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2 (Table; includes other efficacy results). Treatment-related AEs of any grade/grade 3-5 occurred in 57%/16% in C1, 60%/15% in C2, and 71%/17% in C3. 1 pt in each cohort died of a treatment-related AE (C1, sepsis; C2, unknown; C3, immune-related pneumonitis). Conclusions: With additional follow-up, pembro monotherapy continued to show antitumor activity and disease control in pts with RECIST-measurable and bone-predominant mCRPC previously treated with both NHA and docetaxel. Pts experienced durable responses. Safety was consistent with the known safety profile of pembro. Clinical trial information: NCT02787005. [Table: see text]
KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel.
Authors: Stein Mark N. , Fong Lawrence , Mega Anthony E. , Lam Elaine Tat , Heyburn John W. , GUTIERREZ ANDRES A. , Parsi Megan , Vangala Surya , Haas Naomi B. 
Published: February 2020

126 Background: ADXS-PSA, an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), is currently being evaluated in combination with pembrolizumab as a treatment for progressive metastatic castration-resistant prostate cancer (mCRPC) in the phase 1/2 KEYNOTE-046 trial (Part B). Methods: A total of 37 patients received 1x109 CFU + 200 mg pembro IV every 3 wks, for up to 2 yrs or until progression/toxicity. Results: At entry, patients were ~70 yrs with median a Gleason score of 9, and bone predominant disease (70%). MSI-High was negative in 36 pts who were able to be tested. Eighteen (48.6%) patients had received prior docetaxel, 15 pts of whom (83.3%) had also received 1-2 next generation hormonal agents (NGHAs). Nineteen (51.3%) had not received prior docetaxel and 16 of these pts (84.2%) had received 1-2 NGHAs. Overall, 16 out of 37 pts (43%) had a decreased PSA post-BL with 6/37 (16%) pts achieving a confirmed PSA reduction ≥50% from baseline. The median OS (months) for the whole group (37 pts) was 33.6 m (95% CI, range 15.4-33.6 months). The mOS for pts with and without prior exposure to docetaxel was 16 m (5.9 -33.6) and NR at 30 months of follow-up (15.4-NR), respectively. Prolonged survival was observed in pts regardless of prior therapies, microsatellite stable (MSS) status or PSA delta <50% or ≥50%. Conclusions: Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557.