bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Safety, Tolerability, and Pharmacokinetic Profiles of TP0473292 (TS-161), A Prodrug of a Novel Orthosteric mGlu2/3 Receptor Antagonist TP0178894, in Healthy Subjects and Its Antidepressant-Like Effects in Rodents
Authors: Watanabe Mai , Marcy Brian , Hiroki Ayano , Watase Hirotaka , Kinoshita Kohnosuke , Iijima Michihiko , Marumo Toshiyuki , Zarate Carlos A , Chaki Shigeyuki 
Published: September 2021

Abstract

Background
TP0473292 (the active ingredient of TS-161) is a prodrug of a novel metabotropic glutamate (mGlu) 2/3 receptor antagonist being developed for the treatment of patients with depression. This study evaluated the safety, tolerability, and pharmacokinetics of orally administered TS-161 in healthy subjects.

Methods
This was a first-in-human, phase 1, randomized, double-blind, placebo-controlled, single-ascending dose (15–400 mg TS-161) and 10-day multiple-ascending dose (50–150 mg TS-161) study in healthy subjects, conducted from June 2019 through February 2020. Plasma and urine concentrations of the prodrug and its metabolites, and cerebrospinal fluid (CSF) concentrations of the active metabolite TP0178894 were measured to evaluate the pharmacokinetic profiles after oral administration of TS-161.

Results
Following single and multiple doses, TP0473292 was extensively converted into its active metabolite TP0178894. Plasma concentrations of TP0178894 reached peak (Cmax) within 5 hours post dose and declined with a t1/2 &lt;13 hours. Plasma exposures of TP0178894 increased with increasing dose. TP0178894 penetrated into CSF and reached a Cmax of 9.892 ng/mL at a single dose of 100 mg, which was comparable with IC50 values of antagonist activity at mGlu2/3 receptors. The most frequently observed adverse events that showed exposure-related incidence during the study were nausea, vomiting, and dizziness.

Conclusions
The mGlu2/3 receptor antagonist prodrug TP0473292 is safe and well-tolerated, is orally bioavailable in humans with extensive conversion into the active metabolite TP0178894 with sufficient CSF penetration to exert the anticipated pharmacological effects, and is a promising candidate for further clinical development in treatment of patients with depression.
Primary eye care: opportunities for health system strengthening and improved access to services
Authors: Yasmin Sumrana , Schmidt Elena 
Published: September 2021

Abstract
Primary eye care (PEC) is a vital component of primary healthcare (PHC) and is the cornerstone for the progress towards universal eye health coverage. While the concept of PEC is not new, with the increased focus of the global eye-health agenda on equity and people-centred care, it is critical to review experiences of delivering PEC in low- and middle-income countries and to identify common lessons learnt. This commentary builds on the available evidence and focuses specifically on three recently published evaluations of PEC in Sightsavers-supported programmes in Tanzania, Sierra Leone and Pakistan. It argues that systems thinking is critical in the delivery of PEC interventions, as only this approach can ensure that the integration of PEC into PHC is delivered in a comprehensive, coherent and sustainable way.
A commitment and call to strengthen and expand qualitative research efforts to improve the impact of antimicrobial stewardship
Authors: van den Bergh Dena , Brink Adrian 
Published: September 2021

AbstractInadequate recognition of the value of qualitative research in healthcare, notably in antimicrobial stewardship (AMS), in addition to a lack of publishing space in medical journals has prompted JAC-Antimicrobial Resistance to focus on a qualitative series of AMS papers to incite interest in and support for pivotal qualitative approaches that make an indispensable contribution to our understanding of antibiotic use and how to address antimicrobial resistance. In this series, invited authors with diverse backgrounds and considerable expertise address and review intricate and varying qualitative research methods, behaviour change determinants, interventions and qualitative perspectives, with the aim of strengthening commitment and expanding qualitative initiatives to further the impact of AMS globally.
PhenClust, a standalone tool for identifying trends within sets of biological phenotypes using semantic similarity and the Unified Medical Language System metathesaurus
Authors: Wilson Jennifer L , Wong Mike , Stepanov Nicholas , Petkovic Dragutin , Altman Russ 
Published: September 2021

Abstract

Objectives
We sought to cluster biological phenotypes using semantic similarity and create an easy-to-install, stable, and reproducible tool.

Materials and Methods
We generated Phenotype Clustering (PhenClust)—a novel application of semantic similarity for interpreting biological phenotype associations—using the Unified Medical Language System (UMLS) metathesaurus, demonstrated the tool’s application, and developed Docker containers with stable installations of two UMLS versions.

Results
PhenClust identified disease clusters for drug network-associated phenotypes and a meta-analysis of drug target candidates. The Dockerized containers eliminated the requirement that the user install the UMLS metathesaurus.

Discussion
Clustering phenotypes summarized all phenotypes associated with a drug network and two drug candidates. Docker containers can support dissemination and reproducibility of tools that are otherwise limited due to insufficient software support.

Conclusion
PhenClust can improve interpretation of high-throughput biological analyses where many phenotypes are associated with a query and the Dockerized PhenClust achieved our objective of decreasing installation complexity.
Pollen Treated with a Combination of Agrochemicals Commonly Applied During Almond Bloom Reduces the Emergence Rate and Longevity of Honey Bee (Hymenoptera: Apidae) Queens
Authors: Ricke Dylan F , Lin Chia-Hua , Johnson Reed M 
Published: September 2021

Abstract
Honey bee (Apis mellifera L.) colonies that pollinate California’s almond orchards are often exposed to mixtures of agrochemicals. Although agrochemicals applied during almond bloom are typically considered bee-safe when applied alone, their combined effects to honey bees are largely untested. In recent years, beekeepers providing pollination services to California’s almond orchards have reported reductions in queen quality during and immediately after bloom, raising concerns that pesticide exposure may be involved. Previous research identified a synergistic effect between the insecticide active ingredient chlorantraniliprole and the fungicide active ingredient propiconazole to lab-reared worker brood, but their effects to developing queens are unknown. To test the individual and combined effects of these pesticides on the survival and emergence of developing queens, we fed worker honey bees in closed queen rearing boxes with pollen artificially contaminated with formulated pesticides containing these active ingredients as well as the spray adjuvant Dyne-Amic, which contains both organosilicone and alkyphenol ethoxylate. The translocation of pesticides from pesticide-treated pollen into the royal jelly secretions of nurse bees was also measured. Despite consistently low levels of all pesticide active ingredients in royal jelly, the survival of queens from pupation to 7 d post-emergence were reduced in queens reared by worker bees fed pollen containing a combination of formulated chlorantraniliprole (Altacor), propiconazole (Tilt), and Dyne-Amic, as well as the toxic standard, diflubenzuron (Dimilin 2L), applied in isolation. These results support recommendations to protect honey bee health by avoiding application of pesticide tank-mixes containing insecticides and adjuvants during almond bloom.
Capillary hemangioma in the external auditory canal
Authors: Jeong Junhui 
Published: September 2021

Abstract
Hemangioma is a benign vascular soft tissue tumor. It is the most common soft tissue tumor in children and &gt;60% of hemangiomas occur in the head and neck region. However, these tumors are rare in the external auditory canal (EAC). This case report describes a case of capillary hemangioma in the EAC in a woman 54 years of age. With the patient under local anesthesia in microscopic surgery, the mass was excised completely via a transcanal approach. If there is a cystic and pinkish mass in the EAC with symptoms of bleeding or pulsatile tinnitus, hemangioma should be considered. For symptomatic hemangioma, complete surgical excision is necessary and the prognosis is good after excision. Histopathologic confirmation is mandatory after excision.
Binaries are softer than they seem: effects of an external potential on the scattering dynamics of binaries
Authors: Ginat Yonadav Barry , Perets Hagai B 
Published: September 2021

ABSTRACT
Binary evolution is influenced by dynamical scattering with other stars in dense environments. Heggie’s law states that, due to their environments, hard binaries (whose orbital energy surpasses the typical energy of single stars) tend to harden (increase their orbital energy), while soft binaries typically soften. Here, we show that Heggie’s law sometimes needs to be revised, by accounting for an external potential, for example, for binaries in nuclear stellar discs or active galactic nucleus discs, that are affected by the central massive black hole, or binary planetesimals in protoplanetary discs, affected by the host star. We find that in such environments, where the Hill radius is finite, binary-single scattering can have different outcomes. In particular, a three-body encounter could be cut short due to stars being ejected beyond the Hill radius, thereby ceasing to participate in further close interactions. This leads to a systematic difference in the energy changes brought about by the encounter, and in particular slows binary hardening, and even causes some hard binaries to soften, on average, rather than harden. We use our previously derived analytical, statistical solution to the bound chaotic three-body problem to quantitatively characterise the revision of the hardening-softening phase transition and evolution of binaries. We also provide an analytical calculation of the mean hardening rate of binaries in any environment (also reproducing the results of detailed N-body simulations). We show that the latter exhibits a non-trivial dependence on the Hill radius induced by the environment.
Spectral separation of the stochastic gravitational-wave background for LISA in the context of a modulated Galactic foreground
Authors: Boileau Guillaume , Lamberts Astrid , Christensen Nelson , Cornish Neil J , Meyer Renate 
Published: September 2021

ABSTRACT
Within its observational band the Laser Interferometer Space Antenna, LISA, will simultaneously observe orbital modulated waveforms from Galactic white dwarf binaries, a binary black hole produced gravitational-wave background, and potentially a cosmologically created stochastic gravitational-wave background (SGWB). The overwhelming majority of stars end their lives as white dwarfs, making them very numerous in the Milky Way. We simulate Galactic white dwarf binary gravitational-wave emission based on distributions from various mock catalogues and determine a complex waveform from the Galactic foreground with 3.5 × 107 binaries. We describe the effects from the Galactic binary distribution population across mass, position within the Galaxy, core type, and orbital frequency distribution. We generate the modulated Galactic white dwarf signal detected by LISA due to its orbital motion, and present a data analysis strategy to address it. The Fisher Information and Markov Chain Monte Carlo methods give an estimation of the LISA noise and the parameters for the different signal classes. We estimate the detectable limits for the future LISA observation of the SGWB in the spectral domain with the three LISA channels A, E, and T. We simultaneously estimate the Galactic foreground, the astrophysical and cosmological backgrounds. Assuming the expected astrophysical background and a Galactic foreground, a cosmological background energy density of around ΩGW,cosmo ≈ 8 × 10−13 could be detected by LISA. LISA will either detect a cosmologically produced SGWB, or set a limit that will have important consequences.
LeMMINGs III. Thee-MERLIN legacy survey of the Palomar sample: exploring the origin of nuclear radio emission in active and inactive galaxies through the [O iii] – radio connection
Authors: Baldi R D , Williams D R A , Beswick R J , McHardy I , Dullo B T , Knapen J H , Zanisi L , Argo M K , Aalto S , Alberdi A , Baan W A , Bendo G J , Fenech D M , Green D A , Klöckner H-R , Körding E , Maccarone T J , Marcaide J M , Mutie I , Panessa F , Pérez-Torres M A , Romero-Cañizales C , Saikia D J , Saikia P , Shankar F , Spencer R E , Stevens I R , Uttley P , Brinks E , Corbel S , Martí-Vidal I , Mundell C G , Pahari M , Ward M J 
Published: September 2021

ABSTRACTWhat determines the nuclear radio emission in local galaxies? To address this question, we combine optical [O iii] line emission, robust black hole (BH) mass estimates, and high-resolution e-MERLIN 1.5-GHz data, from the LeMMINGs survey, of a statistically complete sample of 280 nearby optically active (LINER and Seyfert) and inactive [H ii and absorption line galaxies (ALGs)] galaxies. Using [O iii] luminosity ($L_{\rm [O\, \small {III}]}$) as a proxy for the accretion power, local galaxies follow distinct sequences in the optical–radio planes of BH activity, which suggest different origins of the nuclear radio emission for the optical classes. The 1.5-GHz radio luminosity of their parsec-scale cores (Lcore) is found to scale with BH mass (MBH) and [O iii] luminosity. Below MBH ∼ 106.5 M⊙, stellar processes from non-jetted H ii galaxies dominate with $L_{\rm core} \propto M_{\rm BH}^{0.61\pm 0.33}$ and $L_{\rm core} \propto L_{\rm [O\, \small {III}]}^{0.79\pm 0.30}$. Above MBH ∼ 106.5 M⊙, accretion-driven processes dominate with $L_{\rm core} \propto M_{\rm BH}^{1.5-1.65}$ and $L_{\rm core} \propto L_{\rm [O\, \small {III}]}^{0.99-1.31}$ for active galaxies: radio-quiet/loud LINERs, Seyferts, and jetted H ii galaxies always display (although low) signatures of radio-emitting BH activity, with $L_{\rm 1.5\, GHz}\gtrsim 10^{19.8}$ W Hz−1 and MBH ≳ 107 M⊙, on a broad range of Eddington-scaled accretion rates ($\dot{m}$). Radio-quiet and radio-loud LINERs are powered by low-$\dot{m}$ discs launching sub-relativistic and relativistic jets, respectively. Low-power slow jets and disc/corona winds from moderately high to high-$\dot{m}$ discs account for the compact and edge-brightened jets of Seyferts, respectively. Jetted H ii galaxies may host weakly active BHs. Fuel-starved BHs and recurrent activity account for ALG properties. In conclusion, specific accretion–ejection states of active BHs determine the radio production and the optical classification of local active galaxies.
Faster Rates of Molecular Sequence Evolution in Reproduction-Related Genes and in Species with Hypodermic Sperm Morphologies
Authors: Wiberg R Axel W , Brand Jeremias N , Schärer Lukas 
Published: September 2021

Abstract
Sexual selection drives the evolution of many striking behaviors and morphologies and should leave signatures of selection at loci underlying these phenotypes. However, although loci thought to be under sexual selection often evolve rapidly, few studies have contrasted rates of molecular sequence evolution at such loci across lineages with different sexual selection contexts. Furthermore, work has focused on separate sexed animals, neglecting alternative sexual systems. We investigate rates of molecular sequence evolution in hermaphroditic flatworms of the genus Macrostomum. Specifically, we compare species that exhibit contrasting sperm morphologies, strongly associated with multiple convergent shifts in the mating strategy, reflecting different sexual selection contexts. Species donating and receiving sperm in every mating have sperm with bristles, likely to prevent sperm removal. Meanwhile, species that hypodermically inject sperm lack bristles, potentially as an adaptation to the environment experienced by hypodermic sperm. Combining functional annotations from the model, Macrostomum lignano, with transcriptomes from 93 congeners, we find genus-wide faster sequence evolution in reproduction-related versus ubiquitously expressed genes, consistent with stronger sexual selection on the former. Additionally, species with hypodermic sperm morphologies had elevated molecular sequence evolution, regardless of a gene’s functional annotation. These genome-wide patterns suggest reduced selection efficiency following shifts to hypodermic mating, possibly due to higher selfing rates in these species. Moreover, we find little evidence for convergent amino acid changes across species. Our work not only shows that reproduction-related genes evolve rapidly also in hermaphroditic animals, but also that well-replicated contrasts of different sexual selection contexts can reveal underappreciated genome-wide effects.
Effectiveness of nutrition interventions on improving diet quality and nutrition knowledge in military populations: a systematic review
Authors: Kullen Charina , Mitchell Lachlan , O’Connor Helen T , Gifford Janelle A , Beck Kathryn L 
Published: September 2021

Abstract

Context
Optimizing nutrition in military groups through improved diet quality and nutrition knowledge is key in supporting the high physical and cognitive demands.

Objective
The objective of this investigation was to systematically review the effectiveness of nutrition interventions among military personnel in improving diet quality and/or nutrition knowledge.

Data Sources
Medline, Embase, CINAHL, and Scopus were searched from the earliest records to May 2020.

Data Extraction
Data were extracted by 2 reviewers. The primary outcomes were diet quality and/or nutrition knowledge.

Data Analysis
Twenty studies were included. The main intervention approaches identified were nutrition education of individuals (i.e., education-based studies; EB) (n = 12), and manipulation of the food service environment (i.e., dining facility studies; DFACs) (n = 8). The most common strategies were face-to-face lectures (n = 8) for EB, and healthier menus (n = 7) and education of catering staff (n = 6) for DFAC interventions. Most studies (18/20) demonstrated favorable within-group effects; however, dietary changes were inconsistent. Five of 10 studies using a comparator group demonstrated positive between-group differences.

Conclusion
Although potential exists for improving diet quality and nutrition knowledge in military populations, the heterogeneity of the studies to date limits conclusions on the most efficacious strategies.
A systematic review of supermarket automated electronic sales data for population dietary surveillance
Authors: Jenneson Victoria L , Pontin Francesca , Greenwood Darren C , Clarke Graham P , Morris Michelle A 
Published: September 2021

Abstract

Context
Most dietary assessment methods are limited by self-report biases, how long they take for participants to complete, and cost of time for dietitians to extract content. Electronically recorded, supermarket-obtained transactions are an objective measure of food purchases, with reduced bias and improved timeliness and scale.

Objective
The use, breadth, context, and utility of electronic purchase records for dietary research is assessed and discussed in this systematic review.

Data sources
Four electronic databases (MEDLINE, EMBASE, PsycINFO, Global Health) were searched. Included studies used electronically recorded supermarket transactions to investigate the diet of healthy, free-living adults.

Data extraction
Searches identified 3422 articles, of which 145 full texts were retrieved and 72 met inclusion criteria. Study quality was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Data analysis
Purchase records were used in observational studies, policy evaluations, and experimental designs. Nutrition outcomes included dietary patterns, nutrients, and food category sales. Transactions were linked to nutrient data from retailers, commercial data sources, and national food composition databases.

Conclusion
Electronic sales data have the potential to transform dietary assessment and worldwide understanding of dietary behavior. Validation studies are warranted to understand limits to agreement and extrapolation to individual-level diets.

Systematic Review Registration
PROSPERO registration no. CRD42018103470
Rethinking Administrative Law for Algorithmic Decision Making
Authors: Williams Rebecca 
Published: September 2021

Abstract
The increasing prevalence of algorithmic decision making (ADM) by public authorities raises a number of challenges for administrative law in the form of technical decisions about the necessary metrics for evaluating such systems, their opacity, the scalability of errors, their use of correlation as opposed to causation and so on. If administrative law is to provide the necessary guidance to enable optimal use of such systems, there are a number of ways in which it will need to become more nuanced and advanced. However, if it is able to rise to this challenge, administrative law has the potential not only to do useful work itself in controlling ADM, but also to support the work of the Information Commissioner’s Office and provide guidance on the interpretation of concepts such as ‘meaningful information’ and ‘proportionality’ within the General Data Protection Regulation.
Solar geoengineering governance: a dynamic framework of farsighted coalition formation
Authors: Heyen Daniel , Lehtomaa Jere 
Published: September 2021

Abstract
Climate interventions with solar geoengineering could reduce climate damages if deployed in a globally coordinated regime. In the absence of such a regime, however, strategic incentives of single actors might result in detrimental outcomes. A well-known concern is that a ‘free-driver’ (Weitzman ML. A voting architecture for the governance of free-driver externalities, with application to geoengineering. Scand J Econ 2015;117:1049–68), the country with the strongest preference for cooling, might unilaterally set the global thermostat to its preferred level, thus imposing damages on others. Governance structures, i.e. more or less formal institutional arrangements between countries, could steer the decentralized geoengineering deployment towards the preferable global outcome. In this paper, we show that the coalition formation literature can make a valuable contribution to assessing the relative merit of different governance schemes. An important feature of the coalition formation literature is the sophisticated dynamic structure. A country pondering whether to leave a coalition anticipates that its departure could spark another process of disintegration among the remaining members of that coalition, which in turn may affect the assessment of whether leaving the coalition is worthwhile in the first place. This dynamic structure thus enables a more realistic picture of what coalitions are likely to form and remain stable. A second important feature of coalition formation models is wide control over the ‘rules of the game’, for instance, which agents need to consent to a transition from one coalitional arrangement to another. This control over the institutional setting allows consistently comparing and discussing various international governance arrangements.