bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing natural killer cell effector function against cancer
Authors: Blunt Matthew D , Khakoo Salim I 
Published: December 2023

Summary
Natural killer (NK) cells are cytotoxic innate lymphoid cells that participate in anti-tumour and anti-viral immune responses. Their ability to rapidly destroy abnormal cells and to enhance the anti-cancer function of dendritic cells, CD8+ T cells, and macrophages makes them an attractive target for immunotherapeutic strategies. The development of approaches that augment NK-cell activation against cancer is currently under intense preclinical and clinical research and strategies include chimeric antigen receptor NK cells, NK-cell engagers, cytokines, and immune checkpoint inhibitors. In this review, we highlight recent advances in NK-cell therapeutic development and discuss their potential to add to our armamentarium against cancer.
Detecting Residual Chronic Salmonella Typhi Carriers on the Road to Typhoid Elimination in Santiago, Chile, 2017–2019
Authors: Lagos Rosanna M , Sikorski Michael J , Hormazábal Juan Carlos , Fernandez Alda , Duarte Sergio , Pasetti Marcela F , Rasko David A , Higginson Ellen , Nkeze Joseph , Kasumba Irene N , Dougan Gordon , Maes Mailis , Lees Andrew , Tennant Sharon M , Levine Myron M 
Published: December 2023

Abstract

Background
In Santiago, Chile, where typhoid had been hyperendemic (1977–1991), we investigated whether residual chronic carriers could be detected among household contacts of non-travel-related typhoid cases occurring during 2017–2019.

Methods
Culture-confirmed cases were classified as autochthonous (domestically acquired) versus travel/immigration related. Household contacts of cases had stool cultures and serum Vi antibody measurements to detect chronic Salmonella Typhi carriers. Whole genome sequences of acute cases and their epidemiologically linked chronic carrier isolates were compared.

Results
Five of 16 autochthonous typhoid cases (31.3%) were linked to 4 chronic carriers in case households; 2 cases (onsets 23 months apart) were linked to the same carrier. Carriers were women aged 69–79 years with gallbladder dysfunction and Typhi fecal excretion; 3 had highly elevated serum anti-Vi titers. Genomic analyses revealed close identity (≤11 core genome single-nucleotide polymorphism [SNP] differences) between case and epidemiologically linked carrier isolates; all were genotypes prevalent in 1980s Santiago. A cluster of 4 additional autochthonous cases unlinked to a carrier was identified based on genomic identity (0-1 SNPs). Travel/immigration isolate genotypes were typical for the countries of travel/immigration.

Conclusions
Although autochthonous typhoid cases in Santiago are currently rare, 5 of 16 such cases (31.3%) were linked to elderly chronic carriers identified among household contacts of cases.
CODA: an open-source platform for federated analysis and machine learning on distributed healthcare data
Authors: Mullie Louis , Afilalo Jonathan , Archambault Patrick , Bouchakri Rima , Brown Kip , Buckeridge David L , Cavayas Yiorgos Alexandros , Turgeon Alexis F , Martineau Denis , Lamontagne François , Lebrasseur Martine , Lemieux Renald , Li Jeffrey , Sauthier Michaël , St-Onge Pascal , Tang An , Witteman William , Chassé Michaël 
Published: December 2023

Abstract

Objectives
Distributed computations facilitate multi-institutional data analysis while avoiding the costs and complexity of data pooling. Existing approaches lack crucial features, such as built-in medical standards and terminologies, no-code data visualizations, explicit disclosure control mechanisms, and support for basic statistical computations, in addition to gradient-based optimization capabilities.

Materials and methods
We describe the development of the Collaborative Data Analysis (CODA) platform, and the design choices undertaken to address the key needs identified during our survey of stakeholders. We use a public dataset (MIMIC-IV) to demonstrate end-to-end multi-modal FL using CODA. We assessed the technical feasibility of deploying the CODA platform at 9 hospitals in Canada, describe implementation challenges, and evaluate its scalability on large patient populations.

Results
The CODA platform was designed, developed, and deployed between January 2020 and January 2023. Software code, documentation, and technical documents were released under an open-source license. Multi-modal federated averaging is illustrated using the MIMIC-IV and MIMIC-CXR datasets. To date, 8 out of the 9 participating sites have successfully deployed the platform, with a total enrolment of &gt;1M patients. Mapping data from legacy systems to FHIR was the biggest barrier to implementation.

Discussion and conclusion
The CODA platform was developed and successfully deployed in a public healthcare setting in Canada, with heterogeneous information technology systems and capabilities. Ongoing efforts will use the platform to develop and prospectively validate models for risk assessment, proactive monitoring, and resource usage. Further work will also make tools available to facilitate migration from legacy formats to FHIR and DICOM.
The evolution of fentanyl-related substances: Prevalence and drug concentrations in postmortem biological specimens at the Miami-Dade Medical Examiner Department
Authors: Martinez Jocelyn , Gonyea Jennifer , Zaney M Elizabeth , Kahl Joseph , Moore Diane M 
Published: December 2023

Abstract
Since 2014, the Miami-Dade Medical Examiner Department (MDME) has observed a drastic increase in the number of fentanyl and fentanyl analog (fentanyl-related substances (FRSs)) fatalities since its introduction into the heroin and cocaine supply. Due to the prevalence of FRS in Miami-Dade County, the MDME toxicology laboratory began documenting each case in which fentanyl and/or a fentanyl analog was identified. Additional information monitored included demographics (age, race and sex), other drugs identified, cause of death (COD) and manner of death (MOD). From 2014 to 2022, the MDME toxicology laboratory analyzed a total of 1,989 cases that tested positive for FRS, of which 1,707 had detectable and/or quantifiable fentanyl concentrations in postmortem cases. The majority of decedents were white males (62%), and the predominant age range was 25–34 years. The most prevalent MOD was accident (93%) with the most common COD listed as acute combined drug toxicity of fentanyl in combination with other drugs (79%). Other drugs found in combination with fentanyl included heroin, cocaine (most prevalent), synthetic cathinones and ethanol. Of all FRS cases, 9% (170 cases) involved fentanyl alone as a COD, while 2% (38 cases) included only fentanyl analogs. Fentanyl concentrations ranged from 1.0 to 1,646 ng/mL in peripheral blood, 1.2 to 449 ng/mL in central blood, 3.2 to 28 ng/mL in donor blood (obtained during tissue harvesting), 1.1 to 108 ng/mL in antemortem blood, 8.5 to 1,130 ng/g in liver and 2.0 to 471 ng/g in brain. Drug concentrations were also reported for an additional eight fentanyl analogs. Considering the prevalence, high potency and constant evolution of FRS, it is important to continuously monitor trends and report drug concentrations in complex medical examiner casework in an effort to educate pathologists, law enforcement and local governments.
Vomeronasal organ volume increases with body size and is dissociated with the loss of a visual signal in Sceloporus lizards
Authors: Erudaitius Anastassia P , Pruett Jake A , Campos Stephanie M , Ossip-Drahos Alison G , Lannoo Susan J , Zúñiga-Vega J Jaime , Vital-García Cuauhcihuatl , Hews Diana K , Martins Emília P , Romero-Diaz Cristina 
Published: December 2023

Abstract
Many organisms communicate using signals in different sensory modalities (multicomponent or multimodal). When one signal or component is lost over evolutionary time, it may be indicative of changes in other characteristics of the signalling system, including the sensory organs used to perceive and process signals. Sceloporus lizards predominantly use chemical and visual signals to communicate, yet some species have lost the ancestral ventral colour patch used in male–male agonistic interactions and exhibit increased chemosensory behaviour. Here, we asked whether evolutionary loss of this sexual signal is associated with larger vomeronasal organ (VNO) volumes (an organ that detects chemical scents) compared with species that have retained the colour patch. We measured VNO coronal section areas of 7–8 adult males from each of 11 Sceloporus species (4 that lost and 7 that retained the colour patch), estimated sensory and total epithelium volume, and compared volumes using phylogenetic analysis of covariance, controlling for body size. Contrary to expectations, we found that species retaining the ventral patch had similar relative VNO volumes as did species that had lost the ancestral patch, and that body size explains VNO epithelium volume. Visual signal loss may be sufficiently compensated for by increased chemosensory behaviour, and the allometric pattern may indicate sensory system trade-offs for large-bodied species.
Microgeographic speciation in a complex of Anatolian bush crickets facilitated by fast evolution of reproductive isolation
Authors: Ortego Joaquín , Kaya Sarp , Çıplak Battal , Lacey Knowles L 
Published: December 2023

Abstract
Identifying the drivers of microgeographic speciation (i.e., speciation over small, local geographic scales) is key to understand the origin of speciose groups. Here, we use genomic data to infer the demographic processes underlying diversification in Poecilimon luschani (Orthoptera: Tettigoniidae), a species complex belonging to the most diverse genus of bush crickets from the Mediterranean region (&gt;170 taxa) that comprises three recognized subspecies with small allopatric distributions in the topographically complex Teke Peninsula, southwestern Anatolia. Phylogenomic reconstructions that include all other taxa within the species group confirmed that subspecies of P. luschani originated from a common ancestor during the Pleistocene, supporting recent (&lt;1 Ma) diversification within a small geographical area (ca. 120 × 80 km). Genetic clustering analyses corroborated the distinctiveness of each subspecies and the cohesiveness of their respective populations, with abrupt genetic discontinuities coinciding with contemporary range boundaries. Indeed, our analyses uncovered the presence of two sympatric cryptic sister lineages that diverged &lt;300 ka ago and do not admix despite being co-distributed. Collectively, these results support that all lineages within the complex represent independently evolving entities corresponding to full-fledged species. Statistical evaluation of alternative models of speciation strongly supports a scenario of divergence in isolation followed by a period of limited gene flow during the last glacial period, when all lineages experienced marked expansions according to demographic reconstructions. Our study exemplifies how localized allopatric divergence and fast evolution of reproductive isolation can promote microgeographic speciation and explain the high rates of endemism characterizing biodiversity hotspots.
Positive selection has shaped the evolution of Argentine ant immune genes both in native and introduced supercolonies
Authors: Holmberg Ida , Tolonen Lassi , Paviala Jenni , Pedersen Jes Søe , Helanterä Heikki , Viljakainen Lumi 
Published: December 2023

Abstract
The highly invasive Argentine ant (Linepithema humile) started its colonisation from the species’ native range in South America approximately 150 years ago and has since become one of the major pests in the world. We investigated how the shifts into new ranges have affected the evolution of Argentine ants’ immune genes. To the best of our knowledge, this is the first broadscale population genetic study focusing on ants’ immune genes. We analysed comprehensive targeted-seq data of immune and non-immune genes containing 174 genes from 18 Argentine ant supercolonies covering the species’ native and introduced ranges. We predicted that the immune gene evolution of introduced supercolonies differs from that of the native supercolonies and proposed two different, non-mutually exclusive hypotheses for this: 1) the enemy release hypothesis and 2) the higher pathogen pressure hypothesis – both of which seem to explain the observed evolutionary patterns on their behalf. Our results show that the introduced supercolonies were targeted by weaker selection than natives, but positive selection was evident among supercolonies of both ranges. Moreover, in some cases, such as the antiviral RNAi genes, introduced range supercolonies harboured a higher proportion of positively selected genes than natives. This observation was striking, knowing the recent demographic history and the detected generally lower selection efficacy of introduced supercolonies. In conclusion, it is evident that pathogen pressure is ubiquitous and strongly affects the immune gene evolution in Argentine ants.
Body size evolution in otters distinguished from terrestrial mustelids
Authors: Harano Tomohiro , Kutsukake Nobuyuki 
Published: December 2023

Abstract
Some taxa of mammals live in water, all of which evolved from land-dwelling ancestors. In the family Mustelidae (Mammalia: Carnivora), most species live on land, while otters, comprising the subfamily Lutrinae, inhabit aquatic environments, which include the almost exclusively aquatic sea otters (Enhydra lutris). Thus, the transition from a terrestrial to an aquatic lifestyle has occurred within this family. Despite potentially different selection pressures on body size in aquatic and terrestrial habitats, no divergence in the evolutionary pattern of body size between otters and other mustelids has previously been shown using models of trait evolution on a phylogeny. We applied models that explicitly incorporated lineage-specific directional selection to the evolution of body mass in living mustelids. Using a simulation-based likelihood and approximate Bayesian computation approach, we demonstrated lineage-specific directional selection for larger body mass in otters, which is distinct from other mustelids. There was no evidence of a difference between sea otters and other otters in the strength of directional selection for larger body mass. Additionally, our analyses supported no difference in the rate at which body mass evolves in both directions between otters and other mustelids. These findings suggest that the evolution of body mass in otters is associated with selective advantages of larger size rather than the relaxation of constraints on body size in aquatic habitats, like other aquatic mammals such as sirenians, cetaceans, and pinnipeds.
Dealing with AI-generated works: lessons from the CDPA section 9(3)
Authors: Atilla Söğüt 
Published: December 2023

Abstract
This article aims to provide some input for revising the text of section 9(3) of the Copyright, Designs and Patents Act 1988 (CDPA), without proposing a new provision. Specifically, it addresses the question of how this provision should be construed vis-à-vis Artificial Intelligence (AI)-generated outputs. Although numerous options have been discussed in literature, so far none of them has comprehensively looked at the broader context in which users of generative AI models give instructions and how these prompts could impact issues of subsistence in AI-generated outputs. This article aims to fill that gap. Before suggesting a new framework for reconsidering the provision of section 9(3) CDPA, this contribution briefly revisits the originality, fixation and human authorship requirements, and explains how these are met when AI is involved in creative processes. Next, it questions whether the copyright regime is the appropriate form of protection for AI-generated outputs. Lastly, it provides an examination of the strengths and weaknesses of section 9(3). This article supports the human-centred approach of the CDPA towards authorship of AI-generated works. However, it also suggests that a more nuanced approach should be adopted. Specifically, it contends that under section 9(3), AI-generated works should belong to the user of the AI model giving instructions only as long as such directions to create are sufficiently original themselves for the purposes of copyright protection. Furthermore, de lege ferenda, this distinction should be expressly included in the text of section 9(3).
Antillean manatee (Trichechus manatus manatus Linnaeus, 1758) Tongue Morphology and Adaptive Herbivorous Implications
Authors: Melo Lucas Inácio dos Santos , Matias de Oliveira Radan Elvis , Freitas Caetano de Sousa Ana Caroline , de Oliveira Rysónely Maclay , Lima Mariana Almeida , Fragoso Ana Bernadete Lima , Silva Flávio José de Lima , Attademo Fernanda Loffler Niemeyer , Luna Fábia de Oliveira , Pereira Alexsandra Fernandes , de Oliveira Moacir Franco 
Published: December 2023

Abstract
Morphological study of the tongue is an interesting way of understanding evolutionary processes associated with feeding habits. Therefore, the aim of the present study was to describe the tongue morphology of the Antillean manatee and to understand possible morphological relationships with its way of capturing food. Macroscopic dissections and light and scanning electron microscopy analyses of seven manatee tongues were performed. The tongue in Antillean manatees is a muscular and robust organ, divided into apex, body, and root. It is firmly adhered to the floor of the oral cavity. Lingual papillae were distributed over the entire tongue surface. They were identified as filiform papillae concentrated in the apex. Fungiform papillae were present on the apex and lateral regions. Foliate papillae were located on the dorsolateral portion of the root. Lentiform papillae were located across the dorsal tongue surface. The mucosa was lined by a keratinized stratified squamous epithelium presenting compound tubuloacinar glands and taste buds in the foliate papillae. The tongue of the Antillean manatee is similar to other Sirenia species, both of which share a completely herbivorous diet.
Analysis of Kozai cycles in equal-mass hierarchical triple supermassive black hole mergers in the presence of a stellar cluster
Authors: Hao Wei , Kouwenhoven M B N , Spurzem Rainer , Amaro-Seoane Pau , Mardling Rosemary A , Xu Xiuming 
Published: December 2023

ABSTRACT
Supermassive black holes (SMBHs) play an important role in galaxy evolution. Binary and triple SMBHs can form after galaxy mergers. A third SMBH may accelerate the SMBH merging process, possibly through the Kozai mechanism. We use N-body simulations to analyse oscillations in the orbital elements of hierarchical triple SMBHs with surrounding star clusters in galaxy centres. We find that SMBH triples spend only a small fraction of time in the hierarchical merger phase (i.e. a binary SMBH with a distant third SMBH perturber). Most of the time, the enclosed stellar mass within the orbits of the innermost or the outermost SMBH is comparable to the SMBH masses, indicating that the influence of the surrounding stellar population cannot be ignored. We search for Eccentric Kozai–Lidov (EKL) oscillations for which (i) the eccentricity of the inner binary and inclination are both oscillate and are antiphase or in-phase and (ii) the oscillation period is consistent with EKL time-scale. We find that EKL oscillations are short-lived and rare: the triple SMBH spends around 3 per cent of its time in this phase over the ensemble of simulations, reaching around 8 per cent in the best-case scenario. This suggests that the role of the EKL mechanism in accelerating the SMBH merger process may have been overestimated in previous studies. We follow-up with three-body simulations, using initial conditions extracted from the simulation, and the result can to some extent repeat the observed EKL-like oscillations. This comparison provides clues about why those EKL oscillations with perturbing stars are short-lived.
Black hole–neutron star mergers: using kilonovae to constrain the equation of state
Authors: Mathias L W P , Di Clemente F , Bulla M , Alessandro D 
Published: December 2023

ABSTRACT
The merging of a binary system involving two neutron stars (NSs), or a black hole (BH) and an NS, often results in the emission of an electromagnetic (EM) transient. One component of this EM transient is the epic explosion known as a kilonova (KN). The characteristics of the KN emission can be used to probe the equation of state (EoS) of NS matter responsible for its formation. We predict KN light curves from computationally simulated BH–NS mergers, by using the 3D radiative transfer code possis. We investigate two EoSs spanning most of the allowed range of the mass–radius diagram. We also consider a soft EoS compatible with the observational data within the so-called 2-families scenario in which hadronic stars co-exist with strange stars. Computed results show that the 2-families scenario, characterized by a soft EoS, should not produce a KN unless the mass of the binary components are small (MBH ≤ 6 M⊙ and MNS ≤ 1.4 M⊙) and the BH is rapidly spinning (χBH ≥ 0.3). In contrast, a strong KN signal potentially observable from future surveys (e.g. the Vera Rubin Observatory) is produced in the 1-family scenario for a wider region of the parameter space, and even for non-rotating BHs (χBH = 0) when MBH = 4 M⊙ and MNS = 1.2 M⊙. We also provide a fit that allows for the calculation of the unbound mass from the observed KN magnitude, without running timely and costly radiative transfer simulations. Findings presented in this paper will be used to interpret light curves anticipated during the fourth observing run (O4), of the advanced LIGO, advanced Virgo, and KAGRA interferometers and thus to constrain the EoS of NS matter.
Warm Dark matter constraints from the joint analysis of CMB, Ly α, and global 21 cm data
Authors: Chatterjee Atrideb , Choudhury Tirthankar Roy 
Published: December 2023

ABSTRACT
With the help of our previously built MCMC (Markov chain Monte Carlo)-based parameter estimation package cosmoreionmc, we investigate in detail the potential of 21 cm global signal, when combined with cosmic microwave background (CMB) and observations related to the Quasar (QSO) absorption spectra, to constraint the mass of warm dark matter (WDM) particle. For the first time, we simultaneously vary all the free parameters (mass of WDM particle, cosmological parameters, and astrophysical parameters) in a joint analysis with CMB, observations related to the QSO absorption spectra and 21 cm global signal, to address the long-overlooked issue of the possible degeneracies between the dark matter particle mass mX and cosmological/astrophysical parameters. From the existing CMB and QSO absorption spectra data, we can rule out mX &lt; 2.8 keV at 95 per cent confidence level. Including a mock 21 cm global signal in the redshift range z = 25−5 expected to be observed with upcoming instruments designed for global signal, the forecasted constraint is found to be much tighter mX &gt; 7.7 keV, assuming that the true dark matter model is the usual cold dark matter. In case the mock 21 cm signal is constructed for dark matter particles having mX = 7 keV, our forecasts indicate that (mX/keV)−1 is in the range [0.1, 0.2] (95 per cent confidence level). This implies that the future 21 cm data should allow detection of the WDM particle mass if mX ∼ 7 keV.