bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ensemble‐based predictive mutation testing approach that considers impact of unreached mutants
Authors: Aghamohammadi Alireza , Mirian‐Hosseinabadi Seyed‐Hassan 
Published: June 2021

SummaryPredictive mutation testing (PMT) is a technique to predict whether a mutant is killed, using machine learning approaches. Researchers have proposed various methods for PMT over the years. However, the impact of unreached mutants on PMT is not fully addressed. A mutant is unreached if the statement on which the mutant is generated is not executed by any test cases. We aim at showing that unreached mutants can inflate PMT results. Moreover, we propose an alternative approach to PMT, suggesting a different interpretation for PMT. To this end, we replicated the previous PMT research. We empirically evaluated the suggested approach on 654 Java projects provided by prior literature. Our results indicate that the performance of PMT drastically decreases in terms of area under a receiver operating characteristic curve (AUC) from 0.833 to 0.517. Furthermore, PMT performs worse than random guesses on 27% of the projects. The proposed approach improves the PMT results, achieving the average AUC value of 0.613. As a result, we recommend researchers to remove unreached mutants when reporting the results.
Long non‐coding RNA DUXAP9 promotes hepatocellular carcinoma cell stemness via directly interacting with sox9
Authors: Zeng Ru , Wang Chunyue , Wang Wenyi , Wang Shuangjia 
Published: June 2021

AbstractLong non‐coding RNA (LncRNA) DUXAP9 expression was recently found to be higher in hepatocellular carcinoma (HCC) tissues and cells, and correlated with a shorter overall survival of HCC patients. However, its roles in HCC progression have never been revealed. Here, the roles of DUXAP9 in HCC cell stemness are explored as cancer stem cells (CSCs) contribute to one of the root of cancer progression. We found that DUXAP9 positively regulated HCC cell stemness, as characterized by the change of sphere‐formation ability, ALDH activity and stemness marker expression. Further luciferase reporter, mRNA stability and RNA–RNA in vitro interaction assays indicated that DUXAP9 directly bound to the 3′ untranslated region (UTR) of sox9, enhanced the mRNA stability of sox9 and thus increased sox9 expression. Notably, the effects induced by DUXAP9 on HCC cell stemness depended on sox9 expression. Therefore, this work identifies a novel DUXAP9/sox9 axis essential for HCC cell stemness.
Clinical findings in dogs diagnosed with leptospirosis in England
Authors: Raj Jennifer , Campbell Ruth , Tappin Simon 
Published: June 2021

AbstractBackground: Leptospirosis is a zoonotic disease of worldwide importance. This study describes the clinical findings and outcome of dogs diagnosed with leptospirosis in England.Methods: Retrospective review of medical records of dogs diagnosed with leptospirosis from a single referral hospital located in Eastern England.Results: Thirty‐eight dogs met the inclusion criteria. Clinical signs included inappetence (76%), vomiting (68%), lethargy (58%), polydipsia and polyuria (18%) and abdominal pain (16%). Disease manifestations included hepatic and renal involvement (47%), hepatic only (37%), renal only (16%); no dogs were found to have respiratory involvement. Clinicopathological findings at presentation included anaemia (42%), thrombocytopenia (43%), increased alanine transaminase activity (ALT) (66%), hyperbilirubinemia (55%), azotaemia (68%), hypoalbuminaemia (49%) and glucosuria (32%). Seven serovars ofLeptospira interrogansorLeptospira kirschneri weredetected; the most prevalent was Copenhageni (48%). Seventy‐one percent survived to discharge. Dogs in the non‐surviving group had a higher creatinine at presentation compared to survivors (p= 0.02).Conclusions: Copenhageni was the most prevalent serovar in this population. This supports the use of a vaccine including this serovar, in this region. Renal involvement was associated with reduced survival to discharge. A hepatic only form was common in this population, and leptospirosis should be included as a differential diagnosis for dogs suffering with a hepatopathy. No cases had significant pulmonary involvement, but ongoing clinical vigilance for this disease manifestation is essential.
Computational methods for predicting hotspots at protein–RNA interfaces
Authors: Mei Long‐Can , Hao Ge‐Fei , Yang Guang‐Fu 
Published: June 2021

AbstractProtein–RNA interactions play essential roles in many critical biological events. A comprehensive understanding of the mechanisms underlying these interactions is helpful when studying cellular activities and therapeutic applications. Hotspots are a small portion of residues contributing much toward protein–RNA binding affinity. In pharmaceutical research, the hotspot residues are seen as the best option for designing small molecules to target proteins of therapeutic interest. With the accumulation of experimental data about protein–RNA interactions, computational methods have been produced for hotspot prediction on a large scale. In this review, we first present an overview of the existing databases for protein–RNA binding data. Furthermore, we outline the most adopted computational methods for hotspots prediction in protein–RNA interactions. Finally, we discuss the applications of hotspot prediction.This article is categorized under:
RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition
RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications
RNA Methods > RNA Analyses In Vitro and In Silico
Real-Time Water Movement in a Plant
Authors: Nakanishi Tomoko M. 
Published: June 2021

AbstractThe next approach to research on water was to measure the small amount of water actually moving within a plant. The best method is to utilize radioisotope (RI)-labeled water and measure the radiation from outside of the plant. However, it is rather difficult to label water, since there are only limited kinds of RI for tracing water.When utilizing 18F to trace water movement, another fundamental question to consider was the features that characterize drought-tolerant and drought-sensitive plants. It is natural to suppose that drought-tolerant plants have strong water absorption; therefore, by analyzing the water absorption mechanism of tolerant plants and by introducing this function to sensitive plants, it might be possible to make the sensitive plants more tolerant.However, when water uptake was studied in naturally developed drought-tolerant and drought-sensitive cowpea, selected from 2000 cowpea plants grown in the field of Africa, the result was unexpected. Under normal conditions, the amount of water absorbed by the drought-tolerant strain was much lower than that absorbed by the sensitive strain, as if showing the low capability of water absorption. When a drought condition was introduced, the tolerant strain began to absorb much more water than usual, whereas the sensitive strain could not absorb as much water as before. This result provided us with an important lesson. Analyzing the mechanism of drought tolerance only by comparing the water absorption of tolerant and sensitive plants might not readily reveal the reason for drought tolerance. The features of the naturally produced plants showed us different mechanisms that might not match our expectations developed in the laboratory.Next, we performed water measurements using 15O-labeled water, which has an extremely short half-life of 2 minutes. Here, we found another astonishing result, which was “water circulation” in the plant internode. A tremendous amount of water was always leaking from xylem cells, which had been regarded as a mere pipe to transfer water from the root to the aboveground parts. In another subsequent study, it was shown that the water flowing out from the xylem was pushing out the water already present in the stem and then returning to the xylem again to move upward. The water velocity in the internode was kept constant, and through simulation, it took less than 20 minutes to exchange the water already present in the stem with newly absorbed water.
Real-Time Element Movement in a Plant
Authors: Nakanishi Tomoko M. 
Published: June 2021

AbstractWe developed an imaging method utilizing the available RIs. We developed two types of real-time RI imaging systems (RRIS), one for macroscopic imaging and the other for microscopic imaging. The principle of visualization was the same, converting the radiation to light by a Cs(Tl)I scintillator deposited on a fiber optic plate (FOS). Many nuclides were employed, including 14C, 18F, 22Na, 28Mg, 32P 33P, 35S, 42K, 45Ca, 48V, 54Mn, 55Fe, 59Fe, 65Zn, 86Rb, 109Cd, and 137Cs.Since radiation can penetrate the soil as well as water, the difference between soil culture and water culture was visualized. 137Cs was hardly absorbed by rice roots growing in soil, whereas water culture showed high absorption, which could provide some reassurance after the Fukushima Nuclear Accident and could indicate an important role of soil in firmly adsorbing the radioactive cesium.28Mg and 42K, whose production methods were presented, were applied for RRIS to visualize the absorption image from the roots. In addition to 28Mg and 42K, many nuclides were applied to image absorption in the roots. Each element showed a specific absorption speed and accumulation pattern. The image analysis of the absorption of Mg is presented as an example. Through successive images of the element absorption, phloem flow in the aboveground part of the plant was analyzed. The element absorption was visualized not only in the roots but also in the leaves, a basic study of foliar fertilization.In the case of the microscopic imaging system, a fluorescence microscope was modified to acquire three images at the same time: a light image, fluorescent image, and radiation image. Although the resolution of the image was estimated to be approximately 50 μm, superposition showed the expression site of the transporter gene and the actual 32P-phosphate absorption site to be the same in Arabidopsis roots.
Visualization of 14C-labeled Gas Fixation in a Plant
Authors: Nakanishi Tomoko M. 
Published: June 2021

AbstractWe targeted not only the elements we can supply to the nutrient solution but also carbon dioxide gas to visualize the fixation process and the movement of assimilated carbon in a plant. This is another highlight of our study using real-time RI imaging systems (RRIS). The interesting result was that the route of assimilated carbon was different depending on where the fixation took place. In Arabidopsis, most of the metabolites after photosynthesis were transferred to the tip of the main internode and roots when 14CO2 gas was fixed and photosynthates were produced at rosette leaves, whereas most of the metabolites moved to the tip of the branch internode and hardly moved down to the roots when 14CO2 gas was supplied to the aboveground parts of the plant other than rosette leaves. Interestingly, it was possible to visualize and trace which tissue performed the fixation of 14CO2 gas, i.e., carbon could be traced from the fixation site in tissue to tissue formation. However, especially in the case of 14C imaging, image analysis should be carefully performed because of the self-absorption of the β-rays in tissue. To image 14CO2 gas fixation in larger samples, approximately 50 cm in height, a plastic scintillator was introduced, and the assimilation process of the gas was visualized for rice and maize.
3D Images
Authors: Nakanishi Tomoko M. 
Published: June 2021

AbstractSpatial (3D) image construction from imaging plate (IP) images and the development of the microautography (MAR) method were presented. A rice grain was sliced every 5 μm, IP images were taken for successive slices, and the series of 2D images acquired by an IP were used to construct 3D images. In the case of 109Cd and 137Cs, the spatial distributions in the grain showed that the concentrations increased at the surface of the grain during the maturing process.
Microautoradiography (MAR)
Authors: Nakanishi Tomoko M. 
Published: June 2021

AbstractMAR was developed to increase the resolution of the image for the sliced plant sample. This revised MAR method showed the detailed distribution of 137Cs accumulation in embryos, which indicated that the plumule and radicle, which grow as a meristem of a root or shoot, were protected from the accumulation of heavy elements. Because of daguerreotype imaging, MAR is now hardly used, and the film emulsion is not available. Here, this method was essentially recreated with a revised processing method for both sample preparation and imaging process.
Other Real-Time Movement
Authors: Nakanishi Tomoko M. 
Published: June 2021

AbstractIn the case of root movement, a very interesting phenomenon was found using the Super-HARP camera, which enabled the visualization of root movement in the dark.Although the first data on plants show that the harmful effect is growth inhibition, the first effect of the toxicity was to stop the rotation movement of the roots before growth inhibition occurred.When there was a chemical change in the environment, although the circumnutation of the root tip ceased, the root was able to elongate, and it was interesting that after a while the root movement resumed. In the case of a rice root, one round of movement of the rice root tip showed a constant time of approximately 50 minutes. However, this movement ceased when Al ion was supplied. The time needed for resuming the movement of the root tip was dependent on the Al ion concentration. It is not known what triggers the resumption of the movement of the root tip.
Dark matter freeze-in from semi-production
Authors: Hryczuk Andrzej , Laletin Maxim 
Published: June 2021

Abstract
We study a novel dark matter production mechanism based on the freeze-in through semi-production, i.e. the inverse semi-annihilation processes. A peculiar feature of this scenario is that the production rate is suppressed by a small initial abundance of dark matter and consequently creating the observed abundance requires much larger coupling values than for the usual freeze-in. We provide a concrete example model exhibiting such production mechanism and study it in detail, extending the standard formalism to include the evolution of dark matter temperature alongside its number density and discuss the importance of this improved treatment. Finally, we confront the relic density constraint with the limits and prospects for the dark matter indirect detection searches. We show that, even if it was never in full thermal equilibrium in the early Universe, dark matter could, nevertheless, have strong enough present-day annihilation cross section to lead to observable signals.
Asymptotic factorization of n-particle SU(N) form factors
Authors: Babujian Hrachya M. , Foerster Angela , Karowski Michael 
Published: June 2021

Abstract
We investigate the high energy behavior of the SU(N) chiral Gross-Neveu model in 1 + 1 dimensions. The model is integrable and matrix elements of several local operators (form factors) are known exactly. The form factors show rapidity space clustering, which means factorization, if a group of rapidities is shifted to infinity. We analyze this phenomenon for the SU(N) model. For several operators the factorization formulas are presented explicitly.
Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer’s disease
Authors: Rompicherla Sampath Kumar L. , Arumugam Karthik , Bojja Sree Lalitha , Kumar Nitesh , Rao C. Mallikarjuna 
Published: June 2021

AbstractWith the increasing aging population and progressive nature of the disease, Alzheimer’s disease (AD) poses to be an oncoming epidemic with limited therapeutic strategies. It is characterized by memory loss, behavioral instability, impaired cognitive function, predominantly, cognitive inability manifested due to the accumulation of β-amyloid, with malfunctioned cholinergic system. Rivastigmine, a reversible dual cholinesterase inhibitor, is a more tolerable and widely used choice of drug for AD. However, rivastigmine being hydrophilic and undergoing the first-pass metabolism exhibits low CNS bioavailability. Nanoformulations including liposomes and PLGA nanoparticles can encapsulate hydrophilic drugs and deliver them efficiently to the brain. Besides, the nasal route is receiving considerable attention recently, due to its direct access to the brain. Therefore, the present study attempts to evaluate the pharmacokinetic and pharmacodynamic properties of nasal liposomal and PLGA nanoparticle formulations of rivastigmine in acute scopolamine-induced amnesia and chronic colchicine induced cognitive dysfunction animal models, and validate the best formulation by employing pharmacokinetic and pharmacodynamic (PK-PD) modeling. Nasal liposomal rivastigmine formulation showed the best pharmacokinetic features with rapid onset of action (Tmax = 5 min), higher Cmax (1489.5 ± 620.71), enhanced systemic bioavailability (F = 118.65 ± 23.54; AUC = 35,921.75 ± 9559.46), increased half-life (30.92 ± 8.38 min), and reduced clearance rate (Kel (1/min) = 0.0224 ± 0.006) compared to oral rivastigmine (Tmax = 15 min; Cmax = 56.29 ± 27.05; F = 4.39 ± 1.82; AUC = 1663.79 ± 813.54; t1/2 = 13.48 ± 5.79; Kel (1/min) = 0.0514 ± 0.023). Further, the liposomal formulation significantly rescued the memory deficit induced by scopolamine as well as colchicine superior to other formulations as assessed in Morris water maze and passive avoidance tasks. PK-PD modeling demonstrated a strong correlation between the pharmacokinetic parameters and acetylcholinesterase inhibition of liposomal formulation.
Strategy-proof mechanism design with non-quasi-linear preferences: ex-post revenue maximization for an arbitrary number of objects
Authors: Sakai Ryosuke , Serizawa Shigehiro 
Published: June 2021

AbstractWe consider the multi-object allocation problem with monetary transfers where each agent obtains at most one object (unit-demand). We focus on allocation mechanisms satisfying individual rationality, non-wastefulness, equal treatment of equals, and strategy-proofness. Extending the result of Kazumura et al. (J Econ Theory 188:105036, 2020b), we show that for an arbitrary number of agents and objects, the minimum price Walrasian is the unique ex-post revenue maximizing mechanism among the mechanisms satisfying no subsidy in addition to the four properties, and that no subsidy in this result can be replaced by no bankruptcy on the positive income effect domain.
Mucosal blood flow in the remaining rectal stump is more affected by total than partial mesorectal excision in patients undergoing anterior resection: a key to understanding differing rates of anastomotic leakage?
Authors: Back Erik , Brännström Fredrik , Svensson Johan , Rutegård Jörgen , Matthiessen Peter , Haapamäki Markku M. , Rutegård Martin 
Published: June 2021

Abstract
Purpose
Anterior resection is the procedure of choice for tumours in the mid and upper rectum. Depending on tumour height, a total mesorectal excision (TME) or partial mesorectal excision (PME) can be performed. Low anastomoses in particular have a high risk of developing anastomotic leakage, which might be explained by blood perfusion compromise. A pilot study indicated a worse blood flow in TME patients in an open setting. The aim of this study was to further evaluate perianastomotic blood perfusion changes in relation to TME and PME in a predominantly laparoscopic context.

Method
In this prospective cohort study, laser Doppler flowmetry was used to evaluate the perianastomotic colonic and rectal perfusion before and after surgery. The two surgical techniques were compared in terms of mean differences of perfusion units using a repeated measures ANOVA design, which also enabled interaction analyses between type of mesorectal excision and location of measurement. Anastomotic leakage until 90 days after surgery was reported for descriptive purposes.

Results
Some 28 patients were available for analysis: 17 TME and 11 PME patients. TME patients had a reduced blood perfusion postoperatively compared to PME patients in the aboral posterior area (mean difference: −57 vs 18 perfusion units; p = 0.010). An interaction between mesorectal excision type and anterior/posterior location was detected at the aboral level (p = 0.007). Two patients developed a minor leakage, diagnosed after discharge.

Conclusion
Patients operated on using TME have a decreased blood flow in the aboral posterior quadrant of the rectum postoperatively compared to patients operated on using PME. This might explain differing rates of anastomotic leakage.

Trial registration
ClinicalTrials.gov Identifier: NCT02401100
Finding Temporal Paths Under Waiting Time Constraints
Authors: Casteigts Arnaud , Himmel Anne-Sophie , Molter Hendrik , Zschoche Philipp 
Published: June 2021

AbstractComputing a (short) path between two vertices is one of the most fundamental primitives in graph algorithmics. In recent years, the study of paths in temporal graphs, that is, graphs where the vertex set is fixed but the edge set changes over time, gained more and more attention. A path is time-respecting, or temporal, if it uses edges with non-decreasing time stamps. We investigate a basic constraint for temporal paths, where the time spent at each vertex must not exceed a given duration $$\varDelta $$
Δ
, referred to as $$\varDelta $$
Δ
-restless temporal paths. This constraint arises naturally in the modeling of real-world processes like packet routing in communication networks and infection transmission routes of diseases where recovery confers lasting resistance. While finding temporal paths without waiting time restrictions is known to be doable in polynomial time, we show that the “restless variant” of this problem becomes computationally hard even in very restrictive settings. For example, it is W[1]-hard when parameterized by the distance to disjoint path of the underlying graph, which implies W[1]-hardness for many other parameters like feedback vertex number and pathwidth. A natural question is thus whether the problem becomes tractable in some natural settings. We explore several natural parameterizations, presenting FPT algorithms for three kinds of parameters: (1) output-related parameters (here, the maximum length of the path), (2) classical parameters applied to the underlying graph (e.g., feedback edge number), and (3) a new parameter called timed feedback vertex number, which captures finer-grained temporal features of the input temporal graph, and which may be of interest beyond this work.