bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity of Clinical Severity Scores for Respiratory Syncytial Virus: A Systematic Review
Authors: Sheikh Zakariya , Potter Ellie , Li You , Cohen Rachel A , Dos Santos Gaël , Bont Louis , Nair Harish ,   PROMISE Investigators, Nair Harish , Campbell Harry , Osei-Yeboah Richard , Paget John , Beutels Philippe , Teirlinck Anne , Nohynek Hanna , Bont Louis , Pollard Andrew , Openshaw Peter , Li You , Aerssens Jeroen , Ispas Gabriela , Kumar Veena , Htar Tin , Begier Elizabeth , Atwell Jessica , Vernhes Charlotte , Kramer Rolf , Bangert Mathieu , Dos Santos Gaël , Cohen Rachel , Last Theo , Ahani Bahar , Machin Nuria
Published: October 2023

Background

Respiratory syncytial virus (RSV) is a widespread respiratory pathogen, and RSV-related acute lower respiratory tract infections are the most common cause of respiratory hospitalization in children <2 years of age. Over the last 2 decades, a number of severity scores have been proposed to quantify disease severity for RSV in children, yet there remains no overall consensus on the most clinically useful score.

Methods

We conducted a systematic review of English-language publications in peer-reviewed journals published since January 2000 assessing the validity of severity scores for children (≤24 months of age) with RSV and/or bronchiolitis, and identified the most promising scores. For included articles, (1) validity data were extracted, (2) quality of reporting was assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis checklist (TRIPOD), and (3) quality was assessed using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). To guide the assessment of the validity data, standardized cutoffs were employed, and an explicit definition of what we required to determine a score was sufficiently validated.

Results

Our searches identified 8541 results, of which 1779 were excluded as duplicates. After title and abstract screening, 6670 references were excluded. Following full-text screening and snowballing, 32 articles, including 31 scores, were included. The most frequently assessed scores were the modified Tal score and the Wang Bronchiolitis Severity Score; none of the scores were found to be sufficiently validated according to our definition. The reporting and/or design of all the included studies was poor. The best validated score was the Bronchiolitis Score of Sant Joan de Déu, and a number of other promising scores were identified.

Conclusions

No scores were found to be sufficiently validated. Further work is warranted to validate the existing scores, ideally in much larger datasets.
Adenosine Triphosphate Release From Influenza-Infected Lungs Enhances Neutrophil Activation and Promotes Disease Progression
Authors: Ledderose Carola , Valsami Eleftheria-Angeliki , Elevado Mark , Junger Wolfgang G
Published: October 2023

Background

Adenosine triphosphate (ATP) enhances neutrophil responses, but little is known about the role of ATP in influenza infections.

Methods

We used a mouse influenza model to study if ATP release is associated with neutrophil activation and disease progression.

Results

Influenza infection increased pulmonary ATP levels 5-fold and plasma ATP levels 3-fold vs healthy mice. Adding ATP at those concentrations to blood from healthy mice primed neutrophils and enhanced CD11b and CD63 expression, CD62L shedding, and reactive oxygen species production in response to formyl peptide receptor stimulation. Influenza infection also primed neutrophils in vivo, resulting in formyl peptide receptor–induced CD11b expression and CD62L shedding up to 3 times higher than that of uninfected mice. In infected mice, large numbers of neutrophils entered the lungs. These cells were significantly more activated than the peripheral neutrophils of infected mice and pulmonary neutrophils of healthy mice. Plasma ATP levels of infected mice and influenza disease progression corresponded with the numbers and activation level of their pulmonary neutrophils.

Conclusions

Findings suggest that ATP release from the lungs of infected mice promotes influenza disease progression by priming peripheral neutrophils, which become strongly activated and cause pulmonary tissue damage after their recruitment to the lungs.
Can we predict the influence of inflammation on voriconazole exposure? An overview
Authors: Boglione-Kerrien Christelle , Zerrouki Selim , Le Bot Audrey , Camus Christophe , Marchand Tony , Bellissant Eric , Tron Camille , Verdier Marie-Clémence , Gangneux Jean-Pierre , Lemaitre Florian
Published: October 2023

Voriconazole is a triazole antifungal indicated for invasive fungal infections that exhibits a high degree of inter-individual and intra-individual pharmacokinetic variability. Voriconazole pharmacokinetics is non-linear, making dosage adjustments more difficult. Therapeutic drug monitoring is recommended by measurement of minimum plasma concentrations. Several factors are responsible for the high pharmacokinetic variability of voriconazole: age, feeding (which decreases absorption), liver function, genetic polymorphism of the CYP2C19 gene, drug interactions and inflammation. Invasive fungal infections are indeed very frequently associated with inflammation, which engenders a risk of voriconazole overexposure. Many studies have reviewed this topic in both the adult and paediatric populations, but few studies have focused on the specific point of the prediction, to evaluate the influence of inflammation on voriconazole pharmacokinetics. Predicting the impact of inflammation on voriconazole pharmacokinetics could help optimize antifungal therapy and improve patient management. This review summarizes the existing data on the influence of inflammation on voriconazole pharmacokinetics in adult populations. We also evaluate the role of C-reactive protein, the impact of inflammation on patient metabolic phenotypes, and the tools that can be used to predict the effect of inflammation on voriconazole pharmacokinetics.
In vitro evaluation of the efficacy of 8-hydroxyquinoline derivatives for the control of Phaeomoniella chlamydospora, the causative agent of Petri disease in grapevines
Authors: de Souza Luciana M , Joaquim Angelica R , Gava Angelo , Ficagna Evandro , Almança Marcus A K , Andrade Saulo F , Fuentefria Alexandre M
Published: October 2023

Aim

This study evaluates the in vitro efficacy of 8-hydroxyquinoline (8HQ) derivatives in controlling the phytopathogenic fungus Phaeomoniella chlamydospora.

Methods and results

The in vitro tests assessed the susceptibility to the minimum inhibitory concentration (MIC), checkerboard assay, mycelial growth (MG) inhibition, and EC50 determination. Among the seven agricultural fungicides tested, tebuconazole (TEB) displayed the lowest MIC, 1.01 µg mL−1, followed by captan (CAP), thiophanate methyl (TM), and mancozeb with MICs of 4.06, 5.46, and 10.62 µg mL−1, respectively. The 8HQ derivatives used in this study were clioquinol and PH 151 (PH) with MICs of 1.09 and 2.02 µg mL−1, respectively. PH associated with TEB and CAP showed synergism and inhibited 95.8% of MG at the highest dose. TEB inhibited 100% of MG at the three highest doses, while associated with PH exhibited the lowest EC50 (0.863 + 0.0381 µg mL−1).

Conclusions

We concluded that the 8HQ derivatives tested controlled effectively the P. chlamydospora in vitro. PH associated with CAP and TEB exhibited a synergistic effect. The association between PH and TM was considered indifferent.

Impact Statement

This study expands the list of active ingredients tested against P. chlamydospora, with the PH 151 and clioquinol derivatives being tested for the first time. The in vitro efficacy and synergistic action with other fungicides suggest a potential use as a grapevine wound protectant. This association makes it possible to reduce doses and increase the potency of both drugs, reducing the risk of resistance development and harm to humans and the environment.
Behavioral Health Screening and Follow-Up Services in Pediatric Trauma Centers Across the United States
Authors: Ridings Leigh E , Espeleta Hannah C , Litvitskiy Nicole , Higgins Kristen , Bravoco Olivia , Davidson Tatiana M , Streck Christian J , Kassam-Adams Nancy , Ruggiero Kenneth J
Published: October 2023

Objective

Over 120,000 U.S. children are hospitalized for traumatic injury annually, a major risk factor for behavioral health problems such as acute/posttraumatic stress disorder (PTSD) and depression. Pediatric trauma centers (PTCs) are well positioned to address the recent mandate by the American College of Surgeons Committee on Trauma to screen and refer for behavioral health symptoms. However, most PTCs do not provide screening or intervention, or use varying approaches. The objective of this mixed-methods study was to assess PTCs’ availability of behavioral health resources and identify barriers and facilitators to service implementation following pediatric traumatic injury (PTI).

Methods

Survey data were collected from 83 Level I (75%) and Level II (25%) PTC program managers and coordinators across 36 states. Semistructured, qualitative interviews with participants (N = 24) assessed the feasibility of implementing behavioral health education, screening, and treatment for PTI patients and caregivers.

Results

Roughly half of centers provide behavioral health screening, predominantly administered by nurses for acute stress/PTSD. Themes from qualitative interviews suggest that (1) service provision varies by behavioral health condition, resource, delivery method, and provider; (2) centers are enthusiastic about service implementation including screening, inpatient brief interventions, and follow-up assessment; but (3) require training and lack staff, time, and funding to implement services.

Conclusions

Sustainable, scalable, evidence-based service models are needed to assess behavioral health symptoms after PTI. Leadership investment is needed for successful implementation. Technology-enhanced, stepped-care approaches seem feasible and acceptable to PTCs to ensure the availability of personalized care while addressing barriers to sustainability.
Detangling Associations Between Maternal Depressive Symptoms and Diabetes Relationship Distress With Adolescents’ HbA1c
Authors: Abadula Fayo , Garretson Sydney , Okonkwo Nkemjika , LeStourgeon Lauren M , Jaser Sarah S
Published: October 2023

Objective 

Previous research in families of children with type 1 diabetes demonstrates that maternal depressive symptoms are a known risk factor for poor diabetes outcomes. We sought to examine whether maternal diabetes relationship distress or maternal depressive symptoms were more strongly associated with adolescent glycemic outcomes.

Methods 

Analyses were conducted using data from mothers who consented to screen for a behavioral intervention. The screener included the Patient Health Questionnaire and the Parent Diabetes Distress Scale, Parent/Teen Relationship Distress subscale. Hemoglobin A1c (HbA1c) was extracted from adolescents’ medical records.

Results 

Our sample consisted of 390 maternal caregivers of adolescents with type 1 diabetes aged 11–17. Screening data revealed that 35% of mothers reported clinically significant diabetes distress related to their relationship with their adolescents, and 14% of mothers reported clinically significant depressive symptoms. The adolescents of mothers who reported diabetes relationship distress had significantly higher mean HbA1c levels (9.7 ± 2.2%) compared to those whose mothers were not distressed (8.2 ± 1.8%, d = .72). Similarly, adolescents whose mothers reported clinically significant depressive symptoms had higher mean HbA1c levels (9.6 ± 2.4%) than those whose mothers were not depressed (8.6 ± 2.0%, d = .48). After adjusting for clinical and demographic factors, mothers’ reports of diabetes relationship distress were more strongly associated with adolescents’ HbA1c than maternal depressive symptoms.

Conclusions 

Our findings suggest that screening for maternal distress—particularly distress related to the caregiver–adolescent relationship—could match families with psychosocial support or other resources to improve both psychosocial and glycemic outcomes.
Pathology, virulence-associated gene profiling, antimicrobial susceptibility, and pathogenicity of untypeable capsular serotypes of Pasteurella multocida isolated from slaughtered pigs of India
Authors: Sahoo Monalisa , Baloni Suraj , Thakor Jigarji C , Kumar Pradeep , Thomas Prasad , Nagaleekar Viswas K , Dhama Kuldeep , Singh Rajendra , Singh Karam P , Mani Saminathan , Qureshi Salauddin , Kumar Ajay , Patel Shailesh K , Biswal Jitendra K , Sahoo Nihar R
Published: October 2023

Pasteurella multocida is widely distributed in all pig-rearing countries, affecting the economic viability and profitability of pig production. The present research highlights the molecular characterization and pathology of untypeable capsular serotypes of P. multocida in slaughtered pigs from prominent pig-rearing states of India. The prevalence of Pasteurellosis was 27.17% by Pasteurella multocida specific Pasteurella multocida specific PCR (PM-PCR). assay, while isolation rate was 7.62%. The microscopic lesions of bronchopneumonia, tonsillitis, and the presence of bacterial antigens in immunohistochemistry confirmed P. multocida with pathologies. In capsular typing, the majority of the isolates were untypeable with prevalence of 52.15% and 43.58% in molecular and microbiological methods, respectively. All the isolates showed the uniform distribution of virulence genes such as exbB, nanB, sodC, plpB, and oma87 (100%), while the variations were observed in ptfA, hasR, ptfA, pfhA, hsf-1, and plpE genes. The untypeable isolates showed higher prevalence of hsf-1 gene as compared to others. The untypeable serotypes showed a higher degree of resistance to ampicillin, amoxicillin, and penicillin antibiotics. The mouse pathogenicity testing of untypeable capsular isolates confirmed its pathogenic potential. The higher frequency of pathogenic untypeable isolates with antibiotic resistance profile might pose a serious threat to the pigs, and therefore, preventive measures should be adopted for effective control.
A comparative analysis of quantitative detection methods for viable food-borne pathogens using RT-qPCR and PMA-qPCR
Authors: Wang Guoxiong , Nie Xinyin , Yang Lihong , Liao Hongmei
Published: October 2023

The accurate quantification of viable pathogens in food is crucial for ensuring food safety. This study mainly aimed to investigate the quantification of viable pathogens using PMA-qPCR and RT-qPCR, taking into account bacterial species, food matrices, and inactivation methods. The detection limit of PMA-qPCR for Salmonella serovars in simple matrices, such as culture broth, lake, or tap water, was found to be 102 cells per ml. Regarding the detection of Staphylococcus aureus and Escherichia coli in culture broth, as well as Salmonella in more complex matrices, such as juices and lab-made broth, both methods exhibited a detection limit of 103 cells per ml. Besides that, in adverse situations, there was a risk of overestimating the number of viable pathogens using PMA-qPCR. In addition, a conspicuous discrepancy between the results of PMA-qPCR/RT-qPCR and those of the plate counting assay was observed when Salmonella was exposed to isopropanol, H2O2, NaClO, sonication, or thermosonication. This suggests that it may survive in a viable but non-culturable state and poses a challenge for accurate quantification of viable cells using plate counting assay. Therefore, the results obtained by RT-qPCR were more objective compared to PMA-qPCR due to potential influences from bacteria species, surrounding media, and inactivation methods.
Heckling, Free Speech, and Freedom of Association
Authors: McTernan Emily , Simpson Robert Mark
Published: October 2023

People sometimes use speech to interfere with other people’s speech, as in the case of a heckler sabotaging a lecture with constant interjections. Some people claim that such interference infringes upon free speech. Against this view, we argue that where competing speakers in a public forum both have an interest in speaking, free speech principles should not automatically give priority to the ‘official’ speaker. Given the ideals underlying free speech, heckling speech sometimes deserves priority. But what can we say, then, about situations in which heckling clearly seems to infringe upon people’s civil liberties, in a way that intuitively justifies intervention? In such cases, we argue, heckling infringes upon people’s associative freedom. We present and defend an ethical framework for the institutional management of ‘Speech Fights’, geared around this insight.
Long-term hard X-ray variability properties of Swift-BAT blazars
Authors: Mundo Sergio A , Mushotzky Richard
Published: October 2023

We present results from the first dedicated study in the time domain of the hard X-ray variability behaviour of blazars on long time-scales based on ∼13 yr of continuous hard X-ray data in the 14–195 keV band. We use monthly binned data from the recent 157-month Swift-BAT (Burst Alert Telescope) catalogue to characterize the hard X-ray variability of 127 blazars and search for potential differences between the variability of BL Lacertae objects (BL Lacs) and flat-spectrum radio quasars (FSRQs). A significant portion of the blazars in the sample (∼37  per cent) do not show statistically significant hard X-ray variability on monthly time-scales, which is deeply at odds with previous studies that show that blazars are highly variable in the X-rays and other energy bands on a wide range of time-scales. We also find that, on average, the FSRQs and BL Lacs for which we do detect variability exhibit similar flux variability; this suggests that the variability in these FSRQs is not necessarily driven by variations in the source function of scattered external radiation arriving from extended regions, and that it is instead possibly driven by processes that lead to variations in particle injection. In addition, only five blazars in our sample show significant spectral variability in the long-term light curves. For three blazars, we find that a power law that changes slope on monthly time-scales is sufficient to characterize the variable hard X-ray spectrum, suggesting that, at least for some bright blazars, the long-term spectra in the hard X-rays may be described in a relatively simple fashion.
Dissecting a 30 kpc galactic outflow at z ~ 1.7
Authors: Shaban Ahmed , Bordoloi Rongmon , Chisholm John , Rigby Jane R , Sharma Soniya , Sharon Keren , Tejos Nicolas , Bayliss Matthew B , Barrientos L Felipe , Lopez Sebastian , Ledoux Cédric , Gladders Michael G , Florian Michael K
Published: October 2023

We present the spatially resolved measurements of a cool galactic outflow in the gravitationally lensed galaxy RCS0327 at z ≈ 1.703 using VLT/MUSE IFU observations. We probe the cool outflowing gas, traced by blueshifted Mg ii and Fe ii absorption lines, in 15 distinct regions of the same galaxy in its image-plane. Different physical regions, 5 – 7 kpc apart within the galaxy, drive the outflows at different velocities (Vout ∼ −161 to −240 km s−1), and mass outflow rates ($\dot{M}_{out} \sim 183$ – 527 ${\rm M}_{\odot }\, \mathrm{yr}^{-1}$). The outflow velocities from different regions of the same galaxy vary by 80 km s−1, which is comparable to the variation seen in a large sample of star-burst galaxies in the local universe. Using multiply lensed images of RCS0327, we probe the same star-forming region at different spatial scales (0.5–25 kpc2), we find that outflow velocities vary between ∼ −120 and −242 km s−1, and the mass outflow rates vary between ∼37 and 254 ${\rm M}_{\odot }\, \mathrm{yr}^{-1}$. The outflow momentum flux in this galaxy is ≥ 100% of the momentum flux provided by star formation in individual regions, and outflow energy flux is ≈ 10% of the total energy flux provided by star formation. These estimates suggest that the outflow in RCS0327 is energy driven. This work shows the importance of small scale variations of outflow properties due to the variations of local stellar properties of the host galaxy in the context of galaxy evolution.
The Dark Energy Spectroscopic Instrument: one-dimensional power spectrum from first Ly α forest samples with Fast Fourier Transform
Authors: Ravoux Corentin , Abdul Karim Marie Lynn , Armengaud Eric , Walther Michael , Karaçaylı Naim Göksel , Martini Paul , Guy Julien , Aguilar Jessica Nicole , Ahlen Steven , Bailey Stephen , Bautista Julian , Beltran Sergio Felipe , Brooks David , Cabayol-Garcia Laura , Chabanier Solène , Chaussidon Edmond , Chaves-Montero Jonás , Dawson Kyle , de la Cruz Rodrigo , de la Macorra Axel , Doel Peter , Fanning Kevin , Font-Ribera Andreu , Forero-Romero Jaime , Gontcho A Gontcho Satya , Gonzalez-Morales Alma X , Gordon Calum , Herrera-Alcantar Hiram K , Honscheid Klaus , Iršič Vid , Ishak Mustapha , Kehoe Robert , Kisner Theodore , Kremin Anthony , Landriau Martin , Le Guillou Laurent , Levi Michael , Lukić Zarija , Magneville Christophe , Meisner Aaron , Miquel Ramon , Moustakas John , Mueller Eva-Maria , Muñoz-Gutiérrez Andrea , Napolitano Lucas , Nie Jundan , Niz Gustavo , Palanque-Delabrouille Nathalie , Percival Will , Pérez-Ràfols Ignasi , Pieri Matthew , Poppett Claire , Prada Francisco , Ramírez Pérez César , Rossi Graziano , Sanchez Eusebio , Schlegel David , Schubnell Michael , Seo Hee-Jong , Sinigaglia Francesco , Tan Ting , Tarlé Gregory , Wang Ben , Weaver Benjamin , Yèche Christophe , Zhou Zhimin
Published: October 2023

We present the one-dimensional Ly α forest power spectrum measurement using the first data provided by the Dark Energy Spectroscopic Instrument (DESI). The data sample comprises 26 330 quasar spectra, at redshift z > 2.1, contained in the DESI Early Data Release and the first 2 months of the main survey. We employ a Fast Fourier Transform (FFT) estimator and compare the resulting power spectrum to an alternative likelihood-based method in a companion paper. We investigate methodological and instrumental contaminants associated with the new DESI instrument, applying techniques similar to previous Sloan Digital Sky Survey (SDSS) measurements. We use synthetic data based on lognormal approximation to validate and correct our measurement. We compare our resulting power spectrum with previous SDSS and high-resolution measurements. With relatively small number statistics, we successfully perform the FFT measurement, which is already competitive in terms of the scale range. At the end of the DESI survey, we expect a five times larger Ly α forest sample than SDSS, providing an unprecedented precise one-dimensional power spectrum measurement.
A multishock scenario for the formation of radio relics
Authors: Smolinski David C , Wittor Denis , Vazza Franco , Brüggen Marcus
Published: October 2023

Radio relics are giant sources of diffuse synchrotron radio emission in the outskirts of galaxy clusters that are associated with shocks in the intracluster medium. Still, the origin of relativistic particles that make up relics is not fully understood. For most relics, diffusive shock acceleration (DSA) of thermal electrons is not efficient enough to explain observed radio fluxes. In this paper, we use a magnetohydrodynamic simulation of galaxy clusters in combination with Lagrangian tracers to simulate the formation of radio relics. Using a Fokker–Planck solver to compute the energy spectra of relativistic electrons, we determine the synchrotron emission of the relic. We find that re-acceleration of fossil electrons plays a major role in explaining the synchrotron emission of radio relics. Particles that pass through multiple shocks contribute significantly to the overall luminosity of a radio relic and greatly boost the effective acceleration efficiency. Furthermore, we find that the assumption that the luminosity of a radio relic can be explained with DSA of thermal electrons leads to an overestimate of the acceleration efficiency by a factor of more than 103.
Signatures of cosmic ray heating in 21-cm observables
Authors: Gessey-Jones T , Fialkov A , de Lera Acedo E , Handley W J , Barkana R
Published: October 2023

Cosmic rays generated by supernovae carry away a significant portion of the lifetime energy emission of their parent star, making them a plausible mechanism for heating the early universe intergalactic medium (IGM). Following a review of the existing literature on cosmic ray heating, we develop a flexible model of this heating mechanism for use in 3D seminumerical 21-cm signal simulations and conduct the first investigations of the signatures it imprints on the 21-cm power spectrum and tomographic maps. We find that cosmic ray heating of the IGM is short-ranged, leading to heating clustered around star-forming sites, and a sharp contrast between heated regions of 21-cm emission and unheated regions of absorption. This contrast results in greater small-scale power for cosmic ray heated scenarios compared to what is found for X-ray heating, thus suggesting a way to test the nature of IGM heating with future 21-cm observations. Finally, we find an unexpectedly rich thermal history in models where cosmic rays can only escape efficiently from low-mass haloes, such as in scenarios where these energetic particles originate from population III star supernovae remnants. The interplay of heating and the Lyman–Werner feedback in these models can produce a local peak in the IGM kinetic temperature and, for a limited parameter range, a flattened absorption trough in the global 21-cm signal.
Signatures of a spinning supermassive black hole binary on the mas-scale jet of the quasar S5 1928+738 based on 25 yr of VLBI data
Authors: Kun E , Britzen S , Frey S , Gabányi K É , Gergely L Á
Published: October 2023

In a previous work, we have identified the spin of the dominant black hole of a binary from its jet properties. Analysing Very Long Baseline Array (VLBA) observations of the quasar S5 1928+738, taken at 15-GHz during 43 epochs between 1995.96 and 2013.06, we showed that the inclination angle variation of the inner (<2 mas) jet symmetry axis naturally decomposes into a periodic and a monotonic contribution. The former emerges due to the Keplerian orbital evolution, while the latter is interpreted as the signature of the spin-orbit precession of the jet emitting black hole. In this paper, we revisit the analysis of the quasar S5 1928+738 by including new 15-GHz VLBA observations extending over 29 additional epochs, between 2013.34 and 2020.89. The extended data set confirms our previous findings which are further supported by the flux density variation of the jet. By applying an enhanced jet precession model that can handle arbitrary spin orientations κ with respect to the orbital angular momentum of a binary supermassive black hole system, we estimate the binary mass ratio as ν = 0.21 ± 0.04 for κ = 0 (i.e. when the spin direction is perpendicular to the orbital plane) and as ν = 0.32 ± 0.07 for κ = π/2 (i.e. when the spin lies in the orbital plane). We estimate more precisely the spin precession velocity, halving its uncertainty from $(-0.05\pm 0.02)$ to $(-0.04\pm 0.01)^{\circ }\, \mathrm{yr}^{-1}$.
Pangolin Genomes Offer Key Insights and Resources for the World’s Most Trafficked Wild Mammals
Authors: Heighton Sean P , Allio Rémi , Murienne Jérôme , Salmona Jordi , Meng Hao , Scornavacca Céline , Bastos Armanda D S , Njiokou Flobert , Pietersen Darren W , Tilak Marie-Ka , Luo Shu-Jin , Delsuc Frédéric , Gaubert Philippe
Published: October 2023

Pangolins form a group of scaly mammals that are trafficked at record numbers for their meat and purported medicinal properties. Despite their conservation concern, knowledge of their evolution is limited by a paucity of genomic data. We aim to produce exhaustive genomic resources that include 3,238 orthologous genes and whole-genome polymorphisms to assess the evolution of all eight extant pangolin species. Robust orthologous gene-based phylogenies recovered the monophyly of the three genera and highlighted the existence of an undescribed species closely related to Southeast Asian pangolins. Signatures of middle Miocene admixture between an extinct, possibly European, lineage and the ancestor of Southeast Asian pangolins, provide new insights into the early evolutionary history of the group. Demographic trajectories and genome-wide heterozygosity estimates revealed contrasts between continental versus island populations and species lineages, suggesting that conservation planning should consider intraspecific patterns. With the expected loss of genomic diversity from recent, extensive trafficking not yet realized in pangolins, we recommend that populations be genetically surveyed to anticipate any deleterious impact of the illegal trade. Finally, we produce a complete set of genomic resources that will be integral for future conservation management and forensic endeavors for pangolins, including tracing their illegal trade. These comprise the completion of whole-genomes for pangolins through the hybrid assembly of the first reference genome for the giant pangolin (Smutsia gigantea) and new draft genomes (∼43x–77x) for four additional species, as well as a database of orthologous genes with over 3.4 million polymorphic sites.
Genomic Signatures Associated with Transitions to Viviparity in Cyprinodontiformes
Authors: Yusuf Leeban H , Saldívar Lemus Yolitzi , Thorpe Peter , Macías Garcia Constantino , Ritchie Michael G
Published: October 2023

The transition from oviparity to viviparity has occurred independently over 150 times across vertebrates, presenting one of the most compelling cases of phenotypic convergence. However, whether the repeated, independent evolution of viviparity is driven by redeployment of similar genetic mechanisms and whether these leave a common signature in genomic divergence remains largely unknown. Although recent investigations into the evolution of viviparity have demonstrated striking similarity among the genes and molecular pathways involved across disparate vertebrate groups, quantitative tests for genome-wide convergent have provided ambivalent answers. Here, we investigate the potential role of molecular convergence during independent transitions to viviparity across an order of ray-finned freshwater fish (Cyprinodontiformes). We assembled de novo genomes and utilized publicly available genomes of viviparous and oviparous species to test for molecular convergence across both coding and noncoding regions. We found no evidence for an excess of molecular convergence in amino acid substitutions and in rates of sequence divergence, implying independent genetic changes are associated with these transitions. However, both statistical power and biological confounds could constrain our ability to detect significant correlated evolution. We therefore identified candidate genes with potential signatures of molecular convergence in viviparous Cyprinodontiformes lineages. Motif enrichment and gene ontology analyses suggest transcriptional changes associated with early morphogenesis, brain development, and immunity occurred alongside the evolution of viviparity. Overall, however, our findings indicate that independent transitions to viviparity in these fish are not strongly associated with an excess of molecular convergence, but a few genes show convincing evidence of convergent evolution.
Deciphering Evolutionary Trajectories of Lactate Dehydrogenases Provides New Insights into Allostery
Authors: Robin Adeline Y , Brochier-Armanet Céline , Bertrand Quentin , Barette Caroline , Girard Eric , Madern Dominique
Published: October 2023

Lactate dehydrogenase (LDH, EC.1.1.127) is an important enzyme engaged in the anaerobic metabolism of cells, catalyzing the conversion of pyruvate to lactate and NADH to NAD+. LDH is a relevant enzyme to investigate structure–function relationships. The present work provides the missing link in our understanding of the evolution of LDHs. This allows to explain (i) the various evolutionary origins of LDHs in eukaryotic cells and their further diversification and (ii) subtle phenotypic modifications with respect to their regulation capacity. We identified a group of cyanobacterial LDHs displaying eukaryotic-like LDH sequence features. The biochemical and structural characterization of Cyanobacterium aponinum LDH, taken as representative, unexpectedly revealed that it displays homotropic and heterotropic activation, typical of an allosteric enzyme, whereas it harbors a long N-terminal extension, a structural feature considered responsible for the lack of allosteric capacity in eukaryotic LDHs. Its crystallographic structure was solved in 2 different configurations typical of the R-active and T-inactive states encountered in allosteric LDHs. Structural comparisons coupled with our evolutionary analyses helped to identify 2 amino acid positions that could have had a major role in the attenuation and extinction of the allosteric activation in eukaryotic LDHs rather than the presence of the N-terminal extension. We tested this hypothesis by site-directed mutagenesis. The resulting C. aponinum LDH mutants displayed reduced allosteric capacity mimicking those encountered in plants and human LDHs. This study provides a new evolutionary scenario of LDHs that unifies descriptions of regulatory properties with structural and mutational patterns of these important enzymes.
Low Mutation Load in a Supergene Underpinning Alternative Male Mating Strategies in Ruff (Calidris pugnax)
Authors: Hill Jason , Enbody Erik D , Bi Huijuan , Lamichhaney Sangeet , Lei Weipan , Chen Juexin , Wei Chentao , Liu Yang , Schwochow Doreen , Younis Shady , Widemo Fredrik , Andersson Leif
Published: October 2023

A paradox in evolutionary biology is how supergenes can maintain high fitness despite reduced effective population size, the suppression of recombination, and the expected accumulation of mutational load. The ruff supergene involves 2 rare inversion haplotypes (satellite and faeder). These are recessive lethals but with dominant effects on male mating strategies, plumage, and body size. Sequence divergence to the wild-type (independent) haplotype indicates that the inversion could be as old as 4 million years. Here, we have constructed a highly contiguous genome assembly of the inversion region for both the independent and satellite haplotypes. Based on the new data, we estimate that the recombination event(s) creating the satellite haplotype occurred only about 70,000 yr ago. Contrary to expectations for supergenes, we find no substantial expansion of repeats and only a modest mutation load on the satellite and faeder haplotypes despite high sequence divergence to the non-inverted haplotype (1.46%). The essential centromere protein N (CENPN) gene is disrupted by the inversion and is as well conserved on the inversion haplotypes as on the noninversion haplotype. These results suggest that the inversion may be much younger than previously thought. The low mutation load, despite recessive lethality, may be explained by the introgression of the inversion from a now extinct lineage.
The dual economy, climate change, and the polarization of American politics
Authors: Oatley Thomas
Published: October 2023

This article explores two questions. What generates the political division over climate change policy in the United States? How is the division over climate change policy related to the broader polarization of contemporary American politics? I argue that the geographies of America’s dual economy—the knowledge economy and the carbon economy—and exposure to the climate crisis intersect to generate a new axis of conflict, which I call the carbon–climate cleavage. This cleavage produces political division over climate change and provides materialist elements that accompany the sociocultural factors that shape contemporary polarization. I demonstrate the existence of the cleavage and its impact using data on economic geography, political attitudes on climate change policy, and support for Trump in the 2016 and 2020 presidential elections. The empirical analysis indicates that carbon economy communities oppose climate change policy and support Trump, while knowledge economy residents support climate change policy and oppose Trump.
Three payment methods and the law of tracing
Authors: Chong Conrad
Published: October 2023

The law of tracing is an area of law that develops rapidly. This article analyses the area of law from the perspective of three payment methods (cash, a letter of credit, and overdrawn bank account) in a commercial context. This article extracts two prepositions that clarify the right to conduct a tracing exercise and advocates further exploration of the law of tracing.
From goal to outcome: Analyzing the progression of biomedical sciences PhD careers in a longitudinal study using an expanded taxonomy
Authors: Brown Abigail M. , Meyers Lindsay C. , Varadarajan Janani , Ward Nicholas J. , Cartailler Jean‐Philippe , Chalkley Roger G. , Gould Kathleen L. , Petrie Kimberly A.
Published: October 2023

Biomedical sciences PhDs pursue a wide range of careers inside and outside academia. However, there is little data regarding how career interests of PhD students relate to the decision to pursue postdoctoral training or to their eventual career outcomes. Here, we present the career goals and career outcomes of 1452 biomedical sciences PhDs who graduated from Vanderbilt University between 1997 and 2021. We categorized careers using an expanded three‐tiered taxonomy and flags that delineate key career milestones. We also analyzed career goal changes between matriculation and doctoral defense, and the reasons why students became more‐ or less‐interested in research‐intensive faculty careers. We linked students' career goal at doctoral defense to whether they did a postdoc, the duration of time between doctoral defense and the first non‐training position, the career area of the first non‐training position, and the career area of the job at 10 years after graduation. Finally, we followed individual careers for 10 years after graduation to characterize movement between different career areas over time. We found that most students changed their career goal during graduate school, declining numbers of alumni pursued postdoctoral training, many alumni entered first non‐training positions in a different career area than their goal at doctoral defense, and the career area of the first non‐training position was a good indicator of the job that alumni held 10 years after graduation. Our findings emphasize that students need a wide range of career development opportunities and career mentoring during graduate school to prepare them for futures in research and research‐related professions.
Mechanical Power Correlates With Stress, Strain, and Atelectrauma Only When Normalized to Aerated Lung Size in Patients With Acute Respiratory Distress Syndrome
Authors: Pistillo Néstor , Castelluccio Pablo , Suzuki Ichiro , Castiblanco Lina
Published: October 2023

OBJECTIVES:

First, to investigate whether the severity of acute respiratory distress syndrome (ARDS) influences ventilator-induced lung injury (VILI) risk in ventilated patients with similar mechanical power of respiratory system (MPRS). Second, to determine whether, under these circumstances, there is a relationship between transpulmonary mechanical power (MPTp) normalized to the aerated lung (specific lung mechanical power or SLMP) and VILI risk, and third, to determine whether normalizing MPRS to compliance of respiratory system (CRS) can replace SLMP to bedside.

DESIGN:

Prospective cohort study.

SETTING:

The study was conducted in a tertiary academic ICU.

PATIENTS:

The study included 18 patients with ARDS.

INTERVENTIONS:

Ventilatory settings were adjusted to achieve a similar MPRS.

MEASUREMENTS AND MAIN RESULTS:

Mechanical power was normalized to CRS (specific mechanical power or SMP = MPRS/CRS), and SLMP was calculated as the ratio between MPTp and end-expiratory lung volume (SLMP = MPTp/EELV). The strain was defined as the ratio between tidal volume and EELV (strain = Vt/EELV), stress as transpulmonary pressure at the end of inspiration, and atelectrauma as the difference between expiration and inspiration in the nonaerated lung. Although patients had been ventilated with similar MPRS = 23.75 (23–24) J/min and MPTp = 11.6 (10.8–12.8) J/min, SLMP increased linearly with the fall in Pao
2/Fio
2 (R = –0.83, p = 0.0001). MPRS only correlated positively with VILI-associated mechanisms when normalized to aerated lung size: correlations between SLMP and stress (R = 0.9, R
2 = 0.84, p = 0.00004), strain (R = 0.97, R
2 = 0.94, p < 0.00001) and atelectrauma (R = 0.82, R
2 = 0.70, p = 0.00002), and correlations between SMP and stress (R = 0.86, R
2 = 0.75, p = 0.00001), strain (R = 0.68, R2 = 0.47, p = 0.001) and atelectrauma (R = 0.67, R
2 = 0.46, p = 0.002).

CONCLUSIONS:

The results suggest that normalizing mechanical power to lung-aerated size or CRS may correlate positively with stress, strain, and atelectrauma.
Genetic risk assessment in breast and gynecologic malignancies- what's to know in 2024?
Authors: Kamara Daniella , Silver Erica , Niell-Swiller Mariana
Published: October 2023

Purpose of review

Hereditary cancer risk assessment and counseling have become integral in oncology care, especially in breast and gynecologic malignancies where genetic test results impact management. However, a large number of patients who could benefit from genetic testing are not getting tested. As such, genetic risk assessment and counseling methods have had to evolve to meet the needs of this expanding patient population.

Recent findings

“Mainstreaming” genetic testing is an initiative to incorporate genetic testing into routine cancer care in lieu of the traditional genetic counseling model to improve uptake of testing while minimizing expansion of genetic counselor and clinic resources. These models have performed well in various institutions demonstrating an improvement in clinical efficacy. However, missed opportunities from the preventive care standpoint, a core value of cancer genetics risk assessment, have become apparent. The focus of these models is on the patient's cancer diagnosis and comprehensive/familial genetic risk assessment is not often completed.

Identifying patients at an increased risk of cancer, even in the absence of a hereditary cancer predisposition syndrome, is important in tailoring screening and preventive measures. As we look to the future, we need to critically approach mainstreaming and determine how to reincorporate comprehensive genetic risk assessment into our models.
Is It Appropriate to Completely Eliminate Contact Shielding during CT Examination? A Discourse Based on Experimental Findings
Authors: Chen Jiwei , Tu Jianchun , Huang Shengyan , Zhu Zhenhua , Tu Yu
Published: October 2023

Objective

Through the integration of experimental data and literature, this study examines whether complete elimination of contact shielding during CT examination is warranted, with a particular focus on potential impacts to children's thyroid and pregnant women, as well as limitations associated with contact shielding. Methods: The thermoluminescent dosimeter (TLD) tablets were inserted into the phantom's five organs and tissues. Select fixed exposure, automatic exposure control (AEC), and use contact shielding combined into four experimental modes, with scanning of the phantom's four parts. Obtain the absorbed dose measurements within or outside the FOV. Statistical analysis was conducted using SPSS software. Results: (1) The AEC significantly reduces dose within and outside the FOV, with a dose reduction of 40%–60%. (2) The application of contact shielding outside the FOV significantly reduced the dose adjoin the FOV. (3) Both the use of AEC mode and contact shielding can effectively minimize the dose, with a reduction of 50–80%. (4) The shielding within the FOV may introduce image artifacts or interfere with AEC, the implementation of contact shielding outside FOV provides little reduction in radiation exposure risk through previous literature. (5) Contact shielding exhibits certain drawbacks in all aspects. Conclusion: The utilization of AEC mode in clinical CT should be widely adopted to minimize patient radiation exposure. In general, contact shielding both inside and outside the FOV should be avoided during exposure. However for children under 12 years old with thyroid gland examination, contact shielding could maximally reduce external radiation and may be appropriate. Pregnant women require careful evaluation when considering the use of contact shielding. Contact shielding should not be entirely abandoned.
Overgrowth syndromes, diagnosis and management
Authors: Klein Steven D. , Nisbet Alex , Kalish Jennifer M.
Published: October 2023

Purpose of review

This review will focus on the current knowledge of the diagnosis and management of overgrowth syndromes with specific focus on mosaic conditions and treatment strategies.

Recent findings

With the implementation of massively parallel sequencing, the genetic etiology of many classically described overgrowth syndromes have been identified. More recently, the role of mosaic genetic changes has been well described in numerous syndromes. Furthermore, the role of imprinting and methylation, especially of the 11p15 region, has been shown to be instrumental for growth. Perhaps most importantly, many overgrowth syndromes carry an increased risk of neoplasm formation especially in the first 10 years of life and possibly beyond. The systematic approach to the child with overgrowth will aide in timely diagnosis and efficiently align them with appropriate screening strategies. In some cases, precision medical interventions are available to target the perturbed growth signaling pathways.

The systematic approach to the child with overgrowth aids in the standardization of the diagnostic pathway for these young patients, thereby expediting the diagnostic timeline, enabling rigorous monitoring, and delivering tailored therapeutic interventions.
Transplant tourism – a missed opportunity
Authors: Merhav Hadar
Published: October 2023

Purpose of review

To explore the resurgence of transplant tourism (TT) despite the recent reiteration of the Declaration of Istanbul (DoI) in 2018. As demand grows exponentially and supply remains static, novel approaches to bridging the gap should be explored.

Recent findings

TT is estimated to comprise up to 10% of transplants worldwide. Prosecuting patients seeking organs through TT has been unsuccessful. Extra jurisdictional prosecution of brokers, vendors and institutions participating in illicit TT has been difficult. Resurgence of TT has occurred in both “traditional” and new countries. The public attitude towards TT and paid donation is largely positive. The Iranian experience with state regulated paid donors merits attention and perhaps emulation. Numerous philosophers, ethicists and transplant professionals find it acceptable to promote financial consideration for organ donors.

Acknowledging the autonomy of persons, including poor and vulnerable ones, to receive financial consideration for their sacrifice should not be considered morally reprehensible. Strict international regulation, oversight and legislation should be implemented to assure adequate compensation, donor wellbeing, elimination of brokers and excellent medical care. Implementing such a system internationally may eliminate kidney waiting lists, provide great benefits to vendors, improve transplant facilities in developing countries and provide substantial savings to insurers.