bluuebunny/crossref_metadata_2025_split huggingface dataset:
A quality by design strategy for cocrystal design based on novel computational and experimental screening strategies: part A
Authors: Ross Steven A. , Ward Adam , Basford Patricia , McAllister Mark , Douroumis Dennis 
Published: November 2024

AbstractWhile pharmaceutical Cocrystals have long been acknowledged as a promising method of enhancing a drugs bioavailability, they have not yet experienced widespread industrial adoption on the same scale as other multi-component drugs, such as salts and amorphous solid dispersions. This is partly due to the lack of a being no definitive screening strategy to identify suitable coformers, with the most cocrystal screening strategies heavily relying on trial and error approaches, or through utilizing a multiple and often conflicting, computational screening techniques combined with high material consumption experimental techniques. From the perspective of industry, this can often lead to high material waste and increased costs, encouraging the prioritization of more traditional bioenhancement techniques. Here we present a strategy for the selection of multicomponent systems involving computational modelling for screening of drug– former pairs based on a combination of molecular complementarity and H-bond propensity screening. Jet dispensing printing technology is co-opted as a mechanism for High-Throughput Screening (HTS) of different stoichiometric ratios, as a low material consumption screening strategy. This strategy is presented herein as a Quality by Design (QbD) crystal engineering approach, combined with experimental screening methods to produce cocrystals of a novel 5-Lipoxygenase (5‐LO) inhibitor, PF-04191834 (PF4). Through this methodology, three new cocrystals were indicated for PF4, confirmed via DSC and XRPD, from less than 50 mg of original testing material. Part B of this study will demonstrate the scalability of this technique continuous extrusion.
Graphical Abstract
On Galois covers of a union of zappatic surfaces of type $$R_k$$
Authors: Amram Meirav , Gong Cheng , Mo Jia-Li 
Published: November 2024

AbstractWe investigate the topological structures of Galois covers of a union of two Zappatic surfaces of type $$R_k$$

R
k

. We prove that the Galois covers of such surfaces are simply connected surfaces of general type. We also compute their Chern numbers and topological indices.
Context Matters: Exploring the Structural Relationships Between ICT Usage, Support, Perceived Usefulness, Intention to Use, and Learning Motivation
Authors: Huang Xueqin , Gao Xingjian , Kim Sangmi , Ohno Shiroh 
Published: November 2024

AbstractPrevious research has extensively explored the integration of Information and Communication Technology (ICT) in education. However, much of previous research has not differentiated between the environments where ICT is used, particularly in terms of its perceived usefulness in school versus at home. This gap in understanding the contextual influence of ICT on students’ learning motivation forms the basis for this study. In particular, this research aims to clarify how different environments influence the effectiveness of ICT in motivating students. Using data from 737 high school students, collected through two surveys, and employing Structural Equation Modeling, the study found that ICT usage in schools is positively linked to its perceived usefulness in both school and home environments. Additionally, ICT support from teachers enhances the perceived usefulness of ICT in both contexts. Furthermore, the perceived usefulness of ICT in both school and home environments significantly predicts students’ intentions to use ICT. However, only the perceived usefulness of ICT at home significantly predicts learning motivation, contrary to initial expectations that school-related ICT would also be a significant predictor. These findings suggest that enhancing students’ learning motivation through ICT integration may require more emphasis on the home environment. The implications for educational policy and practice are discussed, emphasizing a more efficient strategy in incorporating ICT into education.
Exploitation’s grounding problem
Authors: Ferguson Benjamin 
Published: November 2024

Abstract
Standard accounts of what makes exploitation wrong ground its wrong in distributive unfairness: when A exploits B he wrongs her by taking a greater share of the benefits from their interaction than he ought. I argue that this standard account does not succeed; distributive unfairness is neither the sole, nor the primary wrong of exploitation. I assume that distributive unfairness is pro tanto wrong. However, I argue that in situations where transactors’ consent to a transaction is morally valid, it is also morally transformative and overrides distributive unfairness’s pro tanto wrong. Thus, wrongful exploitation requires morally invalid consent.
Maternal environmental control of progeny seed physiology: a review of concepts, evidence and mechanism
Authors: Bezodis William , Penfield Steven 
Published: November 2024

AbstractThe environment experienced by a plant before and after reproduction can have a profound effect on the behaviour of the progeny after shedding. Maternal environmental effects on seeds are important for phenology and fitness in plants, especially for bet-hedging reproductive strategies. Maternal tissues that disperse with seeds are important for dormancy in many species, particularly those with coat-imposed dormancy and those that disperse in indehiscent fruits. Maternal nitrogen status, temperature and photoperiod modify maternal tissues and also influence the developing zygote. During seed development on the mother, the progeny may acquire environmental information directly, but there is also evidence for maternal–filial signalling and the epigenetic inheritance of environmental information through the germline.
Revisiting dose-response: concepts of hormesis, toxicological thresholds and data analysis
Authors: Milosevic Luka , Knezevic Stevan Z. 
Published: November 2024

Abstract
Several publications and web-based tools are available in weed science literature to help weed scientists to carry out basic analysis of dose-response studies. Given the nature of the complicated relationship between the explanatory variable (dose as x-axis) evaluated against response variables of interest (y-axis), using regression curves should be the preferred method for handling data analysis. The objective of this manuscript is to provide user-friendly instructions for conducting and analyzing several types of dose-response studies that were lacking in current weed science literature. A better understanding of less commonly used concepts of hormesis and toxicological safety thresholds (no-observable-adverse-effect-level [NOAEL] and lowest-observable-adverse-effect-level [LOAEL]) is needed to help address the potential risks and benefits associated with herbicide use while minimizing environmental impacts. Basic codes available in cost-free R software are provided for data analysis and to foster collaboration among weed scientists.
A Simple Model for the Evaporation of Hydrometeors and Their Isotopes
Authors: de Szoeke Simon P. , Sarkar Mampi , Quiñones Meléndez Estefanía , Blossey Peter N. , Noone David 
Published: November 2024

AbstractCloud condensation and hydrometeor evaporation fractionate stable isotopes of water, enriching liquid with heavy isotopes; whereupon updrafts, downdrafts, and rain vertically redistribute water and its isotopes in the lower troposphere. These vertical water fluxes through the marine boundary layer affect low cloud climate feedback and, combined with isotope fractionation, are hypothesized to explain the depletion of tropical precipitation at higher precipitation rates known as the “amount effect.” Here, an efficient and numerically stable quasi‐analytical model simulates the evaporation of raindrops and enrichment of their isotope composition. It is applied to a drop size distribution and subcloud environment representative of Atlantic trade cumulus clouds. Idealized physics experiments artificially zero out selected processes to discern the separate effects on the isotope ratio of raindrops, of exchange with the environment, evaporation, and kinetic molecular diffusion. A parameterization of size‐dependent molecular and eddy diffusion is formulated that enriches raindrops much more strongly (+5‰ for deuterated water [HDO] and +3.5‰ for O) than equilibrium evaporation as they become smaller than 1 mm. The effect on evaporated vapor is also assessed. Rain evaporation enriches subcloud vapor by +12‰ per mm rain (for HDO), explaining observations of enriched vapor in cold pools sourced by evaporatively cooled downdrafts. Drops smaller than 0.5 mm evaporate completely before falling 700 m in typical subtropical marine boundary layer conditions. The early and complete evaporation of these smaller drops in the rain size distribution enriches the vapor produced by rain evaporation.
Ecological diversification of sea catfishes is accompanied by genome-wide signatures of positive selection
Authors: Rincon-Sandoval Melissa , De-Kayne Rishi , Shank Stephen D. , Pirro Stacy , Ko’ou Alfred , Abueg Linelle , Tracey Alan , Mountcastle Jackie , O’Toole Brian , Balacco Jennifer , Formenti Giulio , Jarvis Erich D. , Arcila Dahiana , Kosakovsky Pond Sergei L. , Davis Aaron , Bloom Devin D. , Betancur-R Ricardo 
Published: November 2024

AbstractHabitat transitions have shaped the evolutionary trajectory of many clades. Sea catfishes (Ariidae) have repeatedly undergone ecological transitions, including colonizing freshwaters from marine environments, leading to an adaptive radiation in Australia and New Guinea alongside non-radiating freshwater lineages elsewhere. Here, we generate and analyze one long-read reference genome and 66 short-read whole genome assemblies, in conjunction with genomic data for 54 additional species. We investigate how three major ecological transitions have shaped genomic variation among ariids over their ~ 50 million-year evolutionary history. Our results show that relatively younger freshwater lineages exhibit a higher incidence of positive selection than their more ancient marine counterparts. They also display a larger disparity in body shapes, a trend that correlates with a heightened occurrence of positive selection on genes associated with body size and elongation. Although positive selection in the Australia and New Guinea radiation does not stand out compared to non-radiating lineages overall, selection across the prolactin gene family during the marine-to-freshwater transition suggests that strong osmoregulatory adaptations may have facilitated their colonization and radiation. Our findings underscore the significant role of selection in shaping the genome and organismal traits in response to habitat shifts across macroevolutionary scales.
Premature mortality analysis of 52,000 deceased cats and dogs exposes socioeconomic disparities
Authors: Farrell Sean , Anderson Katharine , Noble Peter-John Mäntylä , Al Moubayed Noura 
Published: November 2024

AbstractMonitoring mortality rates offers crucial insights into public health by uncovering the hidden impacts of diseases, identifying emerging trends, optimising resource allocation, and informing effective policy decisions. Here, we present a novel approach to analysing premature mortality in companion animals, utilising data from 28,159 deceased dogs and 24,006 deceased cats across the United Kingdom. By employing PetBERT-ICD, an automated large language model (LLM) based International Classification of Disease 11 syndromic classifier, we reveal critical insights into the causes and patterns of premature deaths. Our findings highlight the significant impact of behavioural conditions on premature euthanasia in dogs, particularly in ages one to six. We also identify a 19% increased risk of premature mortality in brachycephalic dog breeds, raising important animal welfare concerns. Our research establishes a strong correlation between socioeconomic status and premature mortality in cats and dogs. Areas with the lowest Index of Multiple Deprivation (IMD) scores show nearly a 50% reduction in the risk of premature mortality across cats and dogs, underscoring the powerful impact that socioeconomic factors can have on pet health and longevity. This research underscores the necessity of examining the socioeconomic disparities affecting animal health outcomes. By addressing these inequities, we can better safeguard the well-being of our companion animals.
Transcriptomic analysis reveals a critical role for activating Gsα mutations in spontaneous feline hyperthyroidism
Authors: Hiron Thomas K. , Aguiar Joana , Williams Jonathan M. , Falcone Sara , Norman Paul A. , Elliott Jonathan , Fowkes Robert C. , Syme Harriet M. , Davison Lucy J. 
Published: November 2024

AbstractFeline hyperthyroidism (FHT) is a debilitating disease affecting > 10% of elderly cats. It is generally characterised by chronic elevation of thyroid hormone in the absence of circulating TSH. Understanding of the molecular pathogenesis of FHT is currently limited. However, FHT shares clinical and histopathological similarities with human toxic multinodular goitre, which has been associated with activating mutations in TSH receptor (TSHR) and Gsα encoding genes. Using RNA-seq transcriptomic analysis of thyroid tissue from hyperthyroid and euthyroid cats, we identified differentially expressed genes and dysregulated pathways in FHT, many of which are downstream of TSHR. In addition, we detected missense variants in thyroid RNA-seq reads that alter the structure of both TSHR and Gsα. All FHT-associated mutations were absent in germline sequence from paired blood samples. Only a small number of hyperthyroid cats demonstrated TSHR variation, however all thyroids from advanced cases of FHT carried at least one missense variant affecting Gsα. The activating nature of the acquired Gsα mutations was demonstrated by increased cAMP production in vitro. These data indicate that constitutive activation of signalling downstream of TSHR is central to the TSH-independent production of thyroid hormone in FHT, offering a novel therapeutic target pathway in this common disease.
Long-term patterns of forearm asymmetry in females of three syntopic bat species and its effects on individual fitness
Authors: Süess Tobias , Kerth Gerald 
Published: November 2024

AbstractFluctuating asymmetry, the non-directional deviation from bilateral symmetry resulting from developmental instability, can indicate early-life environmental stress. While fluctuating asymmetry can affect individual survival and reproductive success, its effect on fitness differs between species. Here, we analyzed up to 27 years of mark-recapture data from 894 RFID tagged individuals of three forest-living bat species in southern Germany to investigate the degree of fluctuating asymmetry in forearm length. In Bechstein’s bats, Myotis bechsteinii, the species with the highest sample size, we furthermore investigated if fluctuating asymmetry has become more frequent over the study period, a time when juvenile bats have grown larger forearms in response to warmer summers. We also investigated whether fluctuating asymmetry affects individual lifespan and lifetime reproductive success in female Myotis bechsteinii. The degree of fluctuating asymmetry clearly exceeding the measurement error estimated on recaptured individuals was similar in all three species (1.8%). In female Myotis bechsteinii, the frequency of fluctuating asymmetry did not increase over the course of the study and even strong asymmetry had no effect on individual reproductive success and life expectancy. Our data suggest that fluctuating asymmetry is a poor predictor of fitness in the female Myotis bechsteinii studied, and is so far unaffected by the warming environment which is leading to larger individuals in our study population.
Cell surface marker heterogeneity in human myeloma cell lines for modeling of disease and therapy
Authors: Behsen Alenka Djarmila , Holien Toril , Micci Francesca , Rye Morten , Rasmussen Jenny Malm , Andersen Kristin , Hess Eli Svorkdal , Børset Magne , Keats Jonathan , Våtsveen Thea Kristin , Misund Kristine 
Published: November 2024

AbstractMultiple myeloma (MM) is a hematological malignancy originating from plasma cells. Genetically, MM is categorized into two subtypes: hyperdiploid and non-hyperdiploid tumors, with distinct chromosomal characteristics. Human myeloma cell lines (HMCLs) are instrumental in understanding MM and identifying therapeutic targets. However, their utility depends on their resemblance to patient-derived cells. We analyzed protein expression of cell surface markers, including myeloma drug targets and immunotherapy-relevant markers, in nine HMCLs using flow cytometry. RNAseq analysis was performed to correlate protein expression with transcriptomic data. While five cell surface markers (CD47, CD49d, CD138, CD269 (BCMA), and GPRC5D) were highly expressed and three (CD19, CD20, and CD117) were low or negative across cell lines, heterogenous expression was observed for the 16 remaining markers. A comparative study with patient-derived transcriptomic data indicated that four of our six in-house HMCLs closely resembled patient disease. Furthermore, our hyperdiploid HMCLs correlated better with hyperdiploid than non-hyperdiploid patient samples. Here, we also describe three previously uncharacterized HMCLs; IH-1, URVIN and FOLE. Our findings underscore the importance of evaluating surface protein expression in HMCLs when modeling MM. The observed variations in expression levels emphasize the need for a strategic selection of cell lines based on the study’s objectives.
Pathogenic PDE12 variants impair mitochondrial RNA processing causing neonatal mitochondrial disease
Authors: Van Haute Lindsey , Páleníková Petra , Tang Jia Xin , Nash Pavel A , Simon Mariella T , Pyle Angela , Oláhová Monika , Powell Christopher A , Rebelo-Guiomar Pedro , Stover Alexander , Champion Michael , Deshpande Charulata , Baple Emma L , Stals Karen L , Ellard Sian , Anselem Olivia , Molac Clémence , Petrilli Giulia , Loeuillet Laurence , Grotto Sarah , Attie-Bitach Tania , Abdenur Jose E , Taylor Robert W , Minczuk Michal 
Published: November 2024

Abstract
Pathogenic variants in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial function. Within this group, an increasing number of families have been identified, where Mendelian genetic disorders implicate defective mitochondrial RNA biology. The PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Here, we report that disease-causing PDE12 variants in three unrelated families are associated with mitochondrial respiratory chain deficiencies and wide-ranging clinical presentations in utero and within the neonatal period, with muscle and brain involvement leading to marked cytochrome c oxidase (COX) deficiency in muscle and severe lactic acidosis. Whole exome sequencing of affected probands revealed novel, segregating bi-allelic missense PDE12 variants affecting conserved residues. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein. Our data suggest that PDE12 regulates mitochondrial RNA processing and its loss results in neurological and muscular phenotypes.
Distributed GRS‐coded differential spatial modulation for half‐duplex cooperative network based on relay optimization and joint decoding
Authors: Chen Chen , Yang Fengfan 
Published: November 2024

AbstractTo ensure the reliable transmission with increased spectral efficiency of the small information block, this article proposes the novel distributed generalized Reed‐Solomon coded differential spatial modulation (DGRSC‐DSM) scheme in the relay cooperation manner. Two different generalized Reed‐Solomon (GRS) codes with identical lengths are deployed at the source and relay, respectively, where the relay utilizes the subcode of the GRS code, which can construct an ultimate code having a unique algebraic structure at the destination. In addition, the Global search algorithm (Algorithm 1) is developed to obtain an optimal selection mode at the relay, resulting in the final code with an optimal code weight enumeration. Since the complexity of this algorithm is extremely high, the low‐complexity Parity‐position local search algorithm (Algorithm 2) is then proposed to get the suboptimal mode. Monte‐Carlo results indicate that there is a minimal disparity in performance between the two proposed algorithms that both effectively enhance the system performance. Moreover, based on the optimized final code and the special construction of GRS code, the novel Smart‐joint decoding algorithm is first presented at the destination which can fully exploit two‐way information data and further lower the bit error rate (BER) of the DGRSC‐DSM scheme. Also, the analytical union bound of the proposed scheme is formulated over the quasi‐static Rayleigh fading channel, which illustrates a tight fit at the high signal‐to‐noise ratio (SNR) regions.
Design and finite element analysis of a high‐performance surface‐permanent magnet synchronous reluctance machine with optimised robustness towards demagnetisation
Authors: Ghorbani Hamidreza , Majidi Behrooz , Benbouzid Mohamed 
Published: November 2024

AbstractThe aim of this paper is to design and Finite Element Analysis (FEA) of a novel rotor topology for a permanent magnet synchronous reluctance machine. According to the advantages and drawbacks of the PMSyncRM and the SPMSM, a conventional PMSyncRM rotor design combined with sur‐face‐mounted magnets is introduced as the SPMSyncRM. The surface‐PM arc size is investigated, so that it is considered as multiplication of an integer coefficient and the angle between two adjacent slots of the stator. The analysis involves simulation of the electromagnetic characteristics and the numerical model of each structure using finite element method. Each E‐Magnetic character is calculated for a better understanding of the benefits of the SPMSyncRM. Applying 2D FEA, the optimised surface‐PM arc size is calculated and the static and dynamic operational behaviour of the SPMSyncRM is simulated. Moreover, short circuit analysis is performed to study the demagnetisation of magnets. All results are reported comparatively considering a conventional PMSyncRM, so that the proposed SPM‐SyncRM topology presents high torque‐power density, lower values of cogging torque, higher values of power factor and efficiency, better static and dynamic performance, and robustness towards demagnetisation.