bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of lotilaner (Credelio™) against experimentally induced infestations of the adult cat flea, Ctenocephalides felis, and flea eggs following oral administration to cats
Authors: Paarlberg Tandy , Karadzovska Daniela , Helbig Rainer 
Published: March 2021

Abstract
Background
Credelio™ (lotilaner; Elanco) is indicated for the treatment of flea and tick infestations on cats at a recommended lotilaner dose rate of 6–24 mg/kg. This study evaluated the efficacy and safety of lotilaner following a single oral administration to cats for the treatment and prevention of adult Ctenocephalides felis fleas and flea egg production under laboratory conditions.

Methods
Two treatment groups of ten cats each were used in this study. One group was treated with lotilaner at a dose rate of 6−9 mg/kg on Day 0 and the other group served as the control group. Each cat was infested with 100 unfed adult fleas on days –1, 6, 13, 20 and 29. At 24 h post-treatment or post-infestation, each cat was combed to remove and count adult live fleas. At each time point, flea eggs were also collected and counted from under each cat cage.

Results
Following a single oral administration of lotilaner at a minimum dose rate of 6 mg/kg (range 6.00−8.57 mg/kg), the lotilaner group displayed 100%, 100%, 99.9%, 99.9% and 99.8% efficacy against adult live flea counts as compared to the control group on Days 1, 7, 14, 21 and 30, respectively. At each time point, adult flea counts from the lotilaner-treated cats were significantly lower (P < 0.0001) than from the control group. A mean flea egg count of 22.6 in the lotilaner-treated cats (compared to 441.7 in the control animals) was observed 24 h post-treatment. No eggs were present from any of the treated cats on Days 7, 14 and 30 and a single egg was detected on a single treated cat on Day 21. One adverse event (regurgitated food) was observed during the study in one treated cat approximately 1 h after dosing.

Conclusions
Lotilaner was well tolerated; only one adverse event was observed in the treated group. Virtually all adult fleas were killed within 24 h post-treatment or post-infestation in cats treated with a single dose of lotilaner as compared to the control group, thus significantly reducing the number of flea eggs being produced for 30 days after treatment.

Graphical Abstract
Neutron: an attention-based neural decompiler
Authors: Liang Ruigang , Cao Ying , Hu Peiwei , Chen Kai 
Published: March 2021

AbstractDecompilation aims to analyze and transform low-level program language (PL) codes such as binary code or assembly code to obtain an equivalent high-level PL. Decompilation plays a vital role in the cyberspace security fields such as software vulnerability discovery and analysis, malicious code detection and analysis, and software engineering fields such as source code analysis, optimization, and cross-language cross-operating system migration. Unfortunately, the existing decompilers mainly rely on experts to write rules, which leads to bottlenecks such as low scalability, development difficulties, and long cycles. The generated high-level PL codes often violate the code writing specifications. Further, their readability is still relatively low. The problems mentioned above hinder the efficiency of advanced applications (e.g., vulnerability discovery) based on decompiled high-level PL codes.In this paper, we propose a decompilation approach based on the attention-based neural machine translation (NMT) mechanism, which converts low-level PL into high-level PL while acquiring legibility and keeping functionally similar. To compensate for the information asymmetry between the low-level and high-level PL, a translation method based on basic operations of low-level PL is designed. This method improves the generalization of the NMT model and captures the translation rules between PLs more accurately and efficiently. Besides, we implement a neural decompilation framework called Neutron. The evaluation of two practical applications shows that Neutron’s average program accuracy is 96.96%, which is better than the traditional NMT model.
The ECM as a driver of heart development and repair
Authors: Derrick Christopher J. , Noël Emily S. 
Published: March 2021

ABSTRACT
The developing heart is formed of two tissue layers separated by an extracellular matrix (ECM) that provides chemical and physical signals to cardiac cells. While deposition of specific ECM components creates matrix diversity, the cardiac ECM is also dynamic, with modification and degradation playing important roles in ECM maturation and function. In this Review, we discuss the spatiotemporal changes in ECM composition during cardiac development that support distinct aspects of heart morphogenesis. We highlight conserved requirements for specific ECM components in human cardiac development, and discuss emerging evidence of a central role for the ECM in promoting heart regeneration.
DNAJB chaperones suppress destabilised protein aggregation via a region distinct from that used to inhibit amyloidogenesis
Authors: McMahon Shannon , Bergink Steven , Kampinga Harm H. , Ecroyd Heath 
Published: March 2021

ABSTRACT
Disturbances to protein homeostasis (proteostasis) can lead to protein aggregation and inclusion formation, processes associated with a variety of neurodegenerative disorders. DNAJB proteins are molecular chaperones that have been identified as potent suppressors of disease-related protein aggregation. In this work, a destabilised isoform of firefly luciferase (R188Q/R261Q Fluc; termed FlucDM) was overexpressed in cells to assess the capacity of DNAJBs to inhibit inclusion formation. Co-expression of all DNAJB proteins tested significantly inhibited the intracellular aggregation of FlucDM. Moreover, we show that DNAJB proteins suppress aggregation by supporting the Hsp70 (HSPA)-dependent degradation of FlucDM via the proteasome. The serine-rich stretch in DNAJB6 and DNAJB8, essential for preventing fibrillar aggregation, is not involved in the suppression of FlucDM inclusion formation. Conversely, deletion of the C-terminal TTK-LKS motif in DNAJB6 and DNAJB8, a region not required to suppress polyglutamine aggregation, abolished the ability to inhibit inclusion formation by FlucDM. Thus, our data suggest that DNAJB6 and DNAJB8 possess two distinct regions for binding substrates, one that is responsible for binding β-hairpins that form during amyloid formation and another that interacts with exposed hydrophobic patches in aggregation-prone clients.
This article has an associated First Person interview with the first author of the paper.
Na+/H+ exchangers differentially contribute to midgut fluid sodium and proton concentration in the sea urchin larva
Authors: Petersen Inga , Chang William W. J. , Hu Marian Y. 
Published: March 2021

ABSTRACT
Regulation of ionic composition and pH is a requisite of all digestive systems in the animal kingdom. Larval stages of the marine superphylum Ambulacraria, including echinoderms and hemichordates, were demonstrated to have highly alkaline conditions in their midgut with the underlying epithelial transport mechanisms being largely unknown. Using ion-selective microelectrodes, the present study demonstrated that pluteus larvae of the purple sea urchin have highly alkaline pH (pH ∼9) and low [Na+] (∼120 mmol l−1) in their midgut fluids, compared with the ionic composition of the surrounding seawater. We pharmacologically investigated the role of Na+/H+ exchangers (NHE) in intracellular pH regulation and midgut proton and sodium maintenance using the NHE inhibitor 5-(n-ethyl-n-isopropyl)amiloride (EIPA). Basolateral EIPA application decreased midgut pH while luminal application via micro-injections increased midgut [Na+], without affecting pH. Immunohistochemical analysis demonstrated a luminal localization of NHE-2 (SpSlc9a2) in the midgut epithelium. Specific knockdown of spslc9a2 using Vivo-Morpholinos led to an increase in midgut [Na+] without affecting pH. Acute acidification experiments in combination with quantitative PCR analysis and measurements of midgut pH and [Na+] identified two other NHE isoforms, Spslc9a7 and SpSlc9a8, which potentially contribute to the regulation of [Na+] and pH in midgut fluids. This work provides new insights into ion regulatory mechanisms in the midgut epithelium of sea urchin larvae. The involvement of NHEs in regulating pH and Na+ balance in midgut fluids shows conserved features of insect and vertebrate digestive systems and may contribute to the ability of sea urchin larvae to cope with changes in seawater pH.
Thirst and drinking in North American watersnakes (Nerodia spp.)
Authors: Edwards Matthew , Sheehy Coleman M. , Fedler Matthew T. , Lillywhite Harvey B. 
Published: March 2021

ABSTRACT
We quantified drinking behavior in three species of North American watersnakes: Nerodia clarkii, which is a marine or brackish water amphibious species, and Nerodiafasciata and Nerodiataxispilota, both freshwater amphibious species. All three species have relatively small and similar thresholds of dehydration (TH, approximately −4% loss of body mass) that elicit thirst and drinking of fresh water. These species have higher thirst sensitivity than several species of hydrophiine and laticaudine sea snakes, which are characterized by much lower TH (greater dehydration, −9% to &lt;−20%). Nerodia clarkii, which is often found in coastal oceanic water, refused to drink seawater, but drank fresh water when dehydrated. In separate trials involving dehydration of N. clarkii and N. fasciata that were concurrently fed fish at regular intervals, snakes eventually refused to eat at TH of approximately −12% of original body mass, but resumed eating after they were allowed to drink fresh water and rehydrate. The drinking behaviors of Nerodia corroborate previous data on the importance of fresh water for drinking, and they complement growing evidence that dietary water does not itself mitigate dehydration in snakes. These new data increase understanding of water relationships in the context of evolutionary transitions from land to sea, and they emphasize the importance of fresh water resources in the conservation of coastal and marine species of reptiles.
Health economic analyses of latent tuberculosis infection screening and preventive treatment among people living with HIV in lower tuberculosis incidence settings: a systematic review
Authors: Baggaley Rebecca F. , Vegvari Carolin , Dimala Christian A. , Lipman Marc , Miller Robert F. , Brown James , Degtyareva Svetlana , White Helena A. , Hollingsworth T. Déirdre , Pareek Manish 
Published: March 2021

Introduction:In lower tuberculosis (TB) incidence countries (<100 cases/100,000/year), screening and preventive treatment (PT) for latent TB infection (LTBI) among people living with HIV (PLWH) is often recommended, yet guidelines advising which groups to prioritise for screening can be contradictory and implementation patchy. Evidence of LTBI screening cost-effectiveness may improve uptake and health outcomes at reasonable cost.Methods:Our systematic review assessed cost-effectiveness estimates of LTBI screening/PT strategies among PLWH in lower TB incidence countries to identify model-driving inputs and methodological differences. Databases were searched 1980-2020. Studies including health economic evaluation of LTBI screening of PLWH in lower TB incidence countries (<100 cases/100,000/year) were included. Study quality was assessed using the CHEERS checklist.Results:Of 2,644 articles screened, nine studies were included. Cost-effectiveness estimates of LTBI screening/PT for PLWH varied widely, with universal screening/PT found highly cost-effective by some studies, while only targeting to high-risk groups (such as those from mid/high TB incidence countries) deemed cost-effective by others. Cost-effectiveness of strategies screening all PLWH from studies published in the past five years varied from US$2828 to US$144,929/quality-adjusted life-year gained (2018 prices). Study quality varied, with inconsistent reporting of methods and results limiting comparability of studies. Cost-effectiveness varied markedly by screening guideline, with British HIV Association guidelines more cost-effective than NICE guidelines in the UK.Discussion:Cost-effectiveness studies of LTBI screening/PT for PLWH in lower TB incidence settings are scarce, with large variations in methods and assumptions used, target populations and screening/PT strategies evaluated. The limited evidence suggests LTBI screening/PT may be cost-effective for some PLWH groups but further research is required, particularly on strategies targeting screening/PT to PLWH at higher risk. Standardisation of model descriptions and results reporting could facilitate reliable comparisons between studies, particularly to identify those factors driving the wide disparity between cost-effectiveness estimates.Registration:PROSPEROCRD42020166338(18/03/2020).
Hierarchical registration of laser point clouds between airborne and
vehicle-borne data considering building eave attributes
Authors: Guo Yadong , Wang Xiankun , Su Dianpeng , Yang Fanlin , Li Guoyu , Qi Chao 
Published: March 2021

Laser point cloud registration is a key step in multisource laser
scanning data fusion and application. Aimed at the problems of fewer
overlapping regional features and the influence of building eaves on
registration accuracy, a hierarchical registration algorithm of laser
point clouds that considers building eave attributes is proposed in
this paper. After extracting the building feature points of airborne
and vehicle-borne light detection and ranging data, the similarity
measurement model is constructed to carry out coarse registration
based on pseudo-conjugate points. To obtain the feature points of the
potential eaves (FPPE), the building contour lines of the
vehicle-borne data are extended using the direction prediction
algorithm. The FPPE data are regarded as the search set, in which the
iterative closest point (ICP) algorithm is employed to match the true
conjugate points between the airborne laser scanning data and
vehicle-borne laser scanning data. The ICP algorithm is used again to
complete the fine registration. To evaluate the registration
performance, the developed method was applied to the data processing
near Shandong University of Science and Technology, Qingdao, China.
The experimental results showed that the FPPE dataset can effectively
address the coarse registration accuracy effects on the convergence of
the iterative ICP. Before considering eave attributes, the mean
registration errors (MREs) of the proposed method in the

x
o
z

plane,

y
o
z

plane, and

x
o
y

plane are 0.318, 0.96, and 0.786 m,
respectively. After considering eave attributes, the MREs decrease to
0.129, 0.187, and 0.169 m, respectively. The developed method can
effectively improve the registration accuracy of the laser point
clouds, which not only solves the problem of matching true conjugate
points under the effects of the eaves but also avoids converging to a
local minimum due to ICP’s poor coarse registration.
Compact OPCPA system seeded by a Cr:ZnS laser for generating tunable femtosecond pulses in the MWIR
Authors: Fuertjes Pia , von Grafenstein Lorenz , Ueberschaer Dennis , Mei Chao , Griebner Uwe , Elsaesser Thomas 
Published: March 2021

A compact mid-wavelength infrared (MWIR) optical parametric chirped pulse amplification (OPCPA) system generates sub-150 fs pulses at wavelengths from 5.4 to 6.8 µm with

>

400

µ

J

energy at a 1 kHz repetition rate. A femtosecond Cr:ZnS master oscillator emitting 40 fs pulses at 2.4 µm seeds both a Ho:YLF regenerative amplifier and a two-stage OPCPA based on

Z
n
G
e

P

2

crystals. The 2.05 µm few-picosecond pump pulses from the Ho:YLF amplifier have an energy of 13.4 mJ. Seed pulses for the OPCPA are generated by soliton self-frequency shifting in a fluoride fiber and are tunable between 2.8 and 3.25 µm with a sub-100 fs duration and few-nanojoule energy. The intense MWIR pulses hold strong potential for applications in ultrafast mid-infrared nonlinear optics and spectroscopy.
Primary vitrectomy for degenerative and tractional lamellar macular holes: A systematic review and meta-analysis
Authors: Parisi Guglielmo , Fallico Matteo , Maugeri Andrea , Barchitta Martina , Agodi Antonella , Russo Andrea , Longo Antonio , Avitabile Teresio , Castellino Niccolò , Bonfiglio Vincenza , Dell’Omo Roberto , Furino Claudio , Cennamo Gilda , Rejdak Robert , Nowomiejska Katarzyna , Toro Mario , Marolo Paola , Ventre Luca , Reibaldi Michele 
Published: March 2021

Purpose
To assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies.

Methods
PubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate the visual change following primary vitrectomy in the degenerative LMH and LHEP group versus the tractional LMH group. A sensitivity analysis excluding the LHEP group was also performed on the primary outcome. Mean difference (MD) in best corrected visual acuity between baseline and post-treatment was calculated, along with 95% confidence interval (CI). Rate of incidence of post-operative full-thickness macular hole (FTMH) was assessed as secondary outcome.

Results
Thirteen studies were included. Pooled analyses including all groups showed a significant visual improvement following vitrectomy (pre-post MD = -0.17;95%CI = -0.22,-0.12;p<0.001), with no difference in visual improvement between the degenerative LMH and LHEP group and the tractional LMH group. The sensitivity analysis excluding LHEP group confirmed no difference in visual change between the degenerative LMH group (pre-post MD = -0.18;95%CI = -0.24,-0.12;p<0.001) and the tractional LMH group (MD = -0.16;95%CI = -0.26,-0.07;p<0.001). The incidence rate of post-operative FTMH was higher in the degenerative LMH and LHEP group than in the tractional LMH group (p = 0.002).

Conclusion
Primary vitrectomy for LMH ensured a favorable visual outcome, with no difference in visual gain between degenerative and tractional LMHs. However, a higher incidence of post-operative FTMHs was found in eyes with the degenerative LMH subtype.
The Legal Impact of Islamic Law in the Identity and Provisions of Qatari Legal System: Conceptual Frame and Legislative Directions
Authors: Abdullah Abdullah 
Published: March 2021

This article examines the Islamic law situation in Qatari law based on a case study to the main concepts, and some special practical issues in Qatari Law. The paper focuses on a conceptual approach to Qatari law and Islamic law in the light of centrality of Islamic law. Furthermore this paper also focuses on the distinctive characteristics of the law compared to the other such as the concept of human behavior in such a way that it has an impact on the penalty in the legal rule as a distinct component. The analysis also pays an attention to a distinction between the legal rules and other social rules in the matter of giving an influence on structure of human behavior. As a matter of fact, this article also tries to give e light on the centrality of Islamic law on Qatari law, especially on the case of taking back of charity (hibah) as an example. The paper ends with conclusion that for Islamic legislation in Qatari law, Islamic Sharia is considered to be the main source and it is needed to develop a legislative and judicial orientations based on Islamic legal rules that regulate transactions in Qatari law.[Artikel ini membahas situasi hukum Islam di dalam hukum Negara Qatar berdasarkan pada studi kasus atas beberapa konsep kunci dan isu praktis dalam hukum Qatar. Tulisan ini fokus pada pendekatan konseptual hukum Qatar dan Syariah Islam berdasarkan pada sentralitas Syari’ah islam. Selain itu, artikel ini juga membahas tentang karakter khusus undang-undang dibanding dengan yang lainnya seperti teori prilaku yang mempunyai pengaruh terhadap penerapan hukumannya. Selain itu, pembahasan tersebut juga mempertimbangkan perbedaannya dibandingkan dengan hukum sosial terkait dengan pengaruh terhadap pembentukan prilaku. Artikel ini juga memberikan penekanan kajian atas sentralitas hukum Islam dan pengaruhnya terhadap konsep undang-undang seperti pengaturan tentang hak menarik kembali dana hibah dalam undang-undang di Qatar. Dalam kesimpulan, artikel ini menyatakan bahwa dalam undang-undang Qatar, hukum Islam menempati posisi yang sentral dan menjadi basis utama dalam pengembangan legislatif dan orientasi yuridis yang didasarkan pada aturan legal Islam dalam pengaturan transaksi dalam undang-undang hukum di Qatar.]
The Sustained Antidepressant Effects of Ketamine Are Independent of the Lateral Habenula
Authors: Zhou Xuelong , Zhang Chenjing , Miao Jiamin , Chen Ziyang , Dong Hongquan , Liu Cunming 
Published: March 2021

Ketamine is known to have a rapid and lasting antidepressant effect. Recent studies have shown that ketamine exerts it rapid antidepressant effect by blocking burst firing in the lateral habenula (LHb). Whether the sustained antidepressant effect of ketamine occurs through the same mechanism has not been explored. Here, using male rats, we found that local infusion of (R,S)-ketamine into the LHb resulted in a rapid antidepressant-like effect 1 h after infusion, which almost returned to baseline levels after 24 h. Intra-LHb injection of (S)-ketamine also showed a significant antidepressant-like effect 1 h after injection, which recovered at 24 h. No significant antidepressant-like effect was found at 1 or 24 h after the administration of (R)-ketamine into the LHb. Injection of (2R,6R)-hydroxynorketamine, a ketamine metabolite, into the LHb did not result in any obvious antidepressant-like effect 1 or 24 h after injection. Systemic administration of (R,S)-ketamine (intraperitoneally) significantly suppressed LHb bursting activity at 1 h, but the inhibitory effect was reversed 24 h after injection. No significant effect of (R,S)-ketamine on miniature excitatory postsynaptic potentials of LHb neurons was found at 1 or 24 h after systemic application. Our study demonstrated that the sustained antidepressant-like effect of ketamine may not depend on burst firing of LHb neurons.SIGNIFICANCE STATEMENTKetamine exerts it rapid antidepressant effect by blocking burst firing in the lateral habenula (LHb). However, whether the sustained antidepressant effect of ketamine occurs through the same mechanism has not been explored. In the present study, we demonstrated that the sustained antidepressant effect of ketamine may not depend on the burst firing of LHb neurons. This finding may lead to a novel perspective on LHb in the antidepressant effect of ketamine.