bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermediate-mass ratio inspirals in merging elliptical galaxies
Authors: Vázquez-Aceves Verónica , Amaro Seoane Pau , Kuvatova Dana , Makukov Maxim , Omarov Chingis , Yurin Denis
Published: November 2022

Close encounters between two initially unbound objects can result in a binary system if enough energy is released as gravitational waves (GWs). We address the scenario in which such encounters occur in merging elliptical galaxies. There is evidence that elliptical galaxies can harbour intermediate-mass black holes (IMBHs). Therefore, these systems are potentially the breeding grounds of sources of GWs corresponding to inspiraling compact objects onto a massive black hole due to the dynamics, the large densities, and the number of compact remnants they contain. We show that this process is efficient for IMBHs with masses ranging from M ∈ (103, 105) M⊙ and results in the formation of intermediate-mass ratio inspirals (IMRIs). We consider a set of IMBHs and smaller black holes with masses m2 ∈ (10, 103) M⊙ to estimate the IMRI formation rate. We find rates ranging between 10−8 and 10−5 yr−1, and the IMRI formation rate per comoving volume in merging galaxies as a function of the redshift. The peak frequencies of the gravitational radiation emitted when these IMRIs are formed are within the detection band of space-borne detectors such as the Laser Interferometer Space Antenna (LISA) and TianQin; taking into account the observable volume of these detectors, the total amount of IMRI detections per year is significant.
Chemically peculiar stars in integrated light stellar population models and local group galaxies
Authors: Worthey Guy , Shi Xiang
Published: November 2022

Integrated light models that incorporate common types of chemically peculiar (CP) stars are assembled using synthetic spectra. Selected spectral features encode significant age information for populations with ages ∼50 Myr < age < ∼2 Gyr. Due to the alleviation of template mismatch, the inclusion of CP star features in model spectra improves the accuracy of recovered stellar population parameters, but we are not able to show that new or unique age information can be extracted from the weak CP features compared to continuum fitting and strong-feature strengths, at least at the present state of the art. An age-extraction routine that recovers two- and three-burst age structures is employed to analyse the spectra of local group galaxies. NGC 224 (M 31) has a stellar population too old for the types of CP stars we examine. NGC 221 (M 32) also shows no CP spectral features. It appears to contain a component at age ∼1 Gyr at 1 per cent by mass in addition to its dominant 4.7 Gyr population. Unlike Sloan Digital Sky Survey galaxy spectrum averages, NGC 205 (M 110) contains no features due to mercury–manganese (HgMn) stars. This excludes the age range associated with HgMn production, and its near-nuclear spectrum is best fitted by a 68 ± 2 Myr population superimposed on an older population with a 1.85 ± 0.1 Gyr component. Both NGC 205 and NGC 221 have an ancient component whose mass is not easy to constrain given the overwhelming light dominance of the younger populations.
Tidally induced velocity gradients in the Milky Way dwarf spheroidal satellites
Authors: Martínez-García Alberto Manuel , del Pino Andrés , Aparicio Antonio
Published: November 2022

We present a kinematic study of six dwarf spheroidal galaxies (dSph) satellites of the Milky Way (MW), namely Carina, Draco, Fornax, Sculptor, Sextans, and Ursa Minor. We combine proper motions (PMs) from the Gaia Data Release 3 (DR3) and line-of-sight velocities (vlos) from the literature to derive their 3D internal kinematics and to study the presence of internal velocity gradients. We find velocity gradients along the line-of-sight for Carina, Draco, Fornax, and Ursa Minor, at ≥1σ level of significance. The value of such gradients appears to be related to the orbital history of the dwarfs, indicating that the interaction with the MW is causing them. Dwarfs that are close to the MW and moving towards their orbits pericentres show, on average, larger velocity gradients. On the other hand, dwarfs that have recently left their orbits pericentres show no significant gradients. Lastly, dwarfs located at large Galactocentric distances show gradients with an intermediate intensity. Our results would indicate that the torque caused by the strong tidal forces exerted by the MW induces a strong velocity gradient when the dwarfs approach their orbits pericentres. During the pericentre passage, the rapid change in the forces direction would disrupt such gradient, which may steadily recover as the galaxies recede. We assess our findings by analysing dwarfs satellites from the TNG50 simulation. We find a significant increase in the intensity of the detected gradients as the satellites approach their pericentre, followed by a sharp drop as they abandon it, supporting our results for the dSphs of the MW.
Is the star-formation rate in z ∼ 6 quasars overestimated?
Authors: Di Mascia Fabio , Carniani Stefano , Gallerani Simona , Vito Fabio , Pallottini Andrea , Ferrara Andrea , Valentini Milena
Published: November 2022

The large total infrared (TIR) luminosities (LTIR; ≳1012 L⊙) observed in z ∼ 6 quasars are generally converted into high star-formation rates (SFRs; $\gtrsim\!{10}^2~{\rm M}_{\odot }\, {\rm yr}^{-1}$) of their host galaxies. However, these estimates rely on the assumption that dust heating is dominated by stellar radiation, neglecting the contribution from the central active galactic nucleus (AGN). We test the validity of this assumption by combining cosmological hydrodynamic simulations with radiative transfer calculations. We find that, when AGN radiation is included in the simulations, the mass (luminosity)-weighted dust temperature in the host galaxies increases from T ≈ 50 K (T ≈ 70 K) to T ≈ 80 K (T ≈ 200 K), suggesting that AGN effectively heats the bulk of dust in the host galaxy. We compute the AGN-host galaxy SFR from the synthetic spectral energy distribution by using standard SFR – LTIR relations, and compare the results with the ‘true’ values in the simulations. We find that the SFR is overestimated by a factor of ≈3 (≳10) for AGN bolometric luminosities of Lbol ≈ 1012 L⊙ (≳1013 L⊙), implying that the SFRs of z ∼ 6 quasars can be overestimated by over an order of magnitude.
Self-organized criticality in solar GeV flares
Authors: Peng Fang-Kun , Wang Fa-Yin , Shu Xin-Wen , Hou Shu-Jin
Published: November 2022

The Sun emits significant flares in X-ray, ultraviolet, and radio wavelengths. It is thought to originate from the magnetic reconnection activity, which is capable of accelerating particles to high energies. The magnetic process can be described by the avalanche model of self-organized criticality (SOC), and it is evidenced by the observation. Here, we study the frequency distribution of fluence, peak flux, and duration time for solar GeV flares detected first by Fermi-Large Area Telescope. Their cumulative distributions show a power-law behaviour. The exponents are also consistent with those derived from the observations at low-energy bands, and follow the predictions of the fractal-diffuse SOC model. In the meantime, the waiting time shows power-law distribution, and agrees a non-stationary Poission process. We then explore the correlation between energy (fluence) and duration time using a two-variable regression analysis. The correlation is found to be $T_{\rm Duration} \propto F_{\rm GeV}^{0.38\pm 0.08}$ with the solar GeV flare sample, which is comparable to that of the solar X-ray flares and gamma-ray bursts (GRBs) and could be understood in an SOC model. These facts suggest that, similar to the physical process accounting for the X-ray emission of solar flares and prompt emission of GRBs, magnetic reconnection may still dominate the energy-release process and particle acceleration for solar flares at GeV energies.
3D detection and characterization of ALMA sources through deep learning
Authors: Delli Veneri Michele , Tychoniec Łukasz , Guglielmetti Fabrizia , Longo Giuseppe , Villard Eric
Published: November 2022

We present a deep learning (DL) pipeline developed for the detection and characterization of astronomical sources within simulated Atacama Large Millimeter/submillimeter Array (ALMA) data cubes. The pipeline is composed of six DL models: a convolutional autoencoder for source detection within the spatial domain of the integrated data cubes, a Recurrent Neural Network (RNN) for denoising and peak detection within the frequency domain, and four residual neural networks (ResNets) for source characterization. The combination of spatial and frequency information improves completeness while decreasing spurious signal detection. To train and test the pipeline, we developed a simulation algorithm able to generate realistic ALMA observations, i.e. both sky model and dirty cubes. The algorithm simulates always a central source surrounded by fainter ones scattered within the cube. Some sources were spatially superimposed in order to test the pipeline deblending capabilities. The detection performances of the pipeline were compared to those of other methods and significant improvements in performances were achieved. Source morphologies are detected with subpixel accuracies obtaining mean residual errors of 10−3 pixel (0.1 mas) and 10−1 mJy beam−1 on positions and flux estimations, respectively. Projection angles and flux densities are also recovered within 10 per cent of the true values for 80 and 73 per cent of all sources in the test set, respectively. While our pipeline is fine-tuned for ALMA data, the technique is applicable to other interferometric observatories, as SKA, LOFAR, VLBI, and VLTI.
Non-COVID-19 deaths in times of pandemic
Authors: Silverio-Murillo Adan , Balmori de la Miyar Jose Roberto , Martínez-Alfaro Alejandra
Published: November 2022

Background and objective

To investigate the effect of the COVID-19 pandemic on non-COVID-19 deaths in Mexico.

Methods

This study analyzes monthly administrative data on 15 different causes of death in Mexico from 2017 to 2020. The effects of the COVID-19 pandemic on non-COVID-19 deaths are conducted using a difference-in-differences methodology and an event study.

Results

The evidence shows mixed results. There is an increase in six causes of death: diabetes (36.8%), hypertension (25.8%), heart attacks (40.9%), bronchitis- asthma (24.2%), anemia (28.6%) and prostate cancer (21.4%). There is a decrease in two causes of death: traffic accidents (8.8%) and HIV (13.8%). There are null effects for seven causes of death: breast cancer, cerebrovascular disease, malnutrition, alcohol-related liver disease, renal insufficiency, homicides and suicides.

Conclusions

The COVID-19 pandemic affected non-COVID-19 deaths caused by diseases that require intensive healthcare services. Conversely, this pandemic reduced social interactions, which contributed to a decrease on deaths such as traffic accidents.
RADON IN DRINKING WATER FROM ALTERNATIVE SOURCES OF WATER SUPPLY IN THE NORTH OF KOSOVO
Authors: Vučković Biljana , Kurilić Sanja Mrazovac , Nikolić-Bujanović Ljiljana , Todorović Nataša , Nikolov Jovana , Radovanović Jelena Živković , Milošević Rade , Jokić Anja
Published: November 2022

In this study, the results of research on radon activity concentrations in natural mineral waters, traditionally used for drinking but also for other needs, in rural and urban households in northern Kosovo are presented. Radon activity concentration in water was measured by the alpha spectrometric method with a RAD7 device. Radon activity concentrations in the 24 waters studied ranged from 1.6 ± 0.5 to 46.3 ± 6.3 Bq l−1, with an average activity concentration of 12.4 ± 2.0 Bq l−1, which was somewhat higher than the EPA recommended maximum activity concentration, but below the WHO recommended maximum. The contribution of radon activity concentrations in water was determined in relation to the total radon activity in air and enclosed space. The estimated annual effective doses of inhalation and ingestion radon from water were 109.4 ± 16.7 and 2.6 ± 0.4 μSv y−1, respectively.
Reviving a successful blunt chest wall injury protocol
Authors: Smith Carolyn , Schneider Melissa , Pitzer Brittney , Hlodash George
Published: November 2022

This article describes a quality improvement project that assessed nurses' knowledge and practices for patients admitted with a blunt chest wall injury and utilized interactive learning to revive the use of the protocol.
The nursing profession circa 2030
Authors: Boston-Leary Katie , Stone Bobbie
Published: November 2022

The COVID-19 pandemic has forced immediate change and hopefully for the better. Navigating through this new world of care delivery warrants developing new maps to reach a new and acceptable normal. This article outlines urgent issues and necessary steps for measurable change, in nursing practice and work environments by 2030.
Repurposing Spinal Distractor to Reduce Pediatric Wrist Fractures
Authors: Uppal Harjot S. , Biama Richard A.
Published: November 2022

Fracture geometry, particularly a jagged bone spike, can present a physical barrier in closed reduction of pediatric distal radius-ulna fractures. When closed reduction of the fracture is not possible, accepting an incomplete reduction and hoping for remodeling, or open reduction, which poses a greater risk for infection and potential physeal injury, are alternative treatment options. The objective of this study was to describe a technique, coined as Percutaneous Skeletal Traction Aided Reduction (P_STAR), for reducing these fractures, thereby eliminating the acceptance of an incomplete reduction and the risks associated with open reduction. In P_STAR, 2 distraction pins are placed 1.5 cm proximal and distal to the fracture site in clearance of the distal radial physis. A shadow-line spinal distractor is then used to distract the pins, reducing the fracture over the irregular impeding fracture geometry. After distraction is released, 1 or 2 K-wires can be percutaneously inserted to transfix the fracture. A video of the technique was also included as Supplemental Digital Content, http://links.lww.com/BTH/A188. When performed on 18 children with distal radius-ulna fractures, P_STAR achieved near anatomic fracture alignment with no nerve or tendon injury, infection, or refracture.
Learning from the past: a short term forecast method for the COVID-19 incidence curve
Authors: Morel Jean-David , Morel Jean-Michel , Alvarez Luis
Published: November 2022

The COVID-19 pandemy has created a radically new situation where most countries provide raw measurements of their daily incidence and disclose them in real time. This enables new machine learning forecast strategies where the prediction might no longer be based just on the past values of the current incidence curve, but could take advantage of observations in many countries. We present such a simple global machine learning procedure using all past daily incidence trend curves. Each of the 27,418 COVID-19 incidence trend curves in our database contains the values of 56 consecutive days extracted from observed incidence curves across 61 world regions and countries. Given a current incidence trend curve observed over the past four weeks, its forecast in the next four weeks is computed by matching it with the first four weeks of all samples, and ranking them by their similarity to the query curve. Then the 28 days forecast is obtained by a statistical estimation combining the values of the 28 last observed days in those similar samples. Using comparison performed by the European Covid-19 Forecast Hub with the current state of the art forecast methods, we verify that the proposed global learning method, EpiLearn, compares favorably to methods forecasting from a single past curve.
Comprehensive Understanding of Hydrogeochemical evaluation of seasonal variability in groundwater quality Dynamics in the Gold Mining Areas of Osun State, Nigeria
Authors: Olalekan Awogbami Stephen , Adewoye Solomon Olayinka , Henry Sawyerr Olawale , Olaniyi Opasola Afolabi , Raimi Morufu Olalekan
Published: November 2022

Background

A crucial issue directly affecting the wellbeing of the human race is water quality. Within a few decades, a greater reliance on groundwater was needed to supply water for drinking, agriculture, and other uses due to the scarcity and contamination of surface water. To forecast its long-term use and increase output, irrigated agriculture requires high-quality water, which must be measured.

Objective

The goals of the current study are to comprehend the hydro-geochemistry, drinking water appropriateness, and occurrence of hydro-geochemistry concepts in the groundwater of the gold mining regions of Osun State, South-West Nigeria.

Method

Standardized analytical methods were used in the research. All sampling, conservation, transportation, and analysis were carried out in accordance with APHA guidelines (2012). To prevent deterioration of the organic compounds, all acquired samples were sent to research laboratory, while maintaining in an icebox.

Results

The study also identifies critical pollutants, affecting the ground water quality within its course through the gold mining areas of Osun State. Finally, Colour, pH, DO, EC, TDS, TSS, TS, Hardness, Magnesium, Nitrate, Phosphate, Lead, Cadmium, Chromium, Manganese, Mercury and Arsenic have been found to be critical parameters for the stretch in each season of this research.

Conclusion

The authors advise developing ongoing systems for monitoring water quality as well as efficient management techniques to prevent excessive groundwater pollution. These findings will therefore aid decision-makers in managing pollution in Osun State’s gold mining zones and better understanding the impact of different seasons on water quality. The findings of this study can serve as a foundation for the future monitoring of the effects of anthropogenic activities on local watercourses when mining companies are developed. This requires consideration in terms of both regulatory measures and proactive initiatives for addressing the ensuing issues in the future. In order to maintain sustainability, a long-term monitoring plan is suggested in this study to be implemented into the groundwater bodies to restore their quality.
FHIR-DHP: A Standardized Clinical Data Harmonisation Pipeline for scalable AI application deployment
Authors: Williams Elena , Kienast Manuel , Medawar Evelyn , Reinelt Janis , Merola Alberto , Ines Klopfenstein Sophie Anne , Flint Anne Rike , Heeren Patrick , Poncette Akira-Sebastian , Balzer Felix , Beimes Julian , Bünau Paul von , Chromik Jonas , Arnrich Bert , Scherf Nico , Niehaus Sebastian
Published: November 2022

Background

Increasing digitalisation in the medical domain gives rise to large amounts of healthcare data which has the potential to expand clinical knowledge and transform patient care if leveraged through artificial intelligence (AI). Yet, big data and AI oftentimes cannot unlock their full potential at scale, owing to non-standardised data formats, lack of technical and semantic data interoperability, and limited cooperation between stakeholders in the healthcare system. Despite the existence of standardised data formats for the medical domain, such as Fast Healthcare Interoperability Resources (FHIR), their prevalence and usability for AI remains limited.

Objective

We developed a data harmonisation pipeline (DHP) for clinical data sets relying on the common FHIR data standard.

Methods

We validated the performance and usability of our FHIR-DHP with data from the MIMIC IV database including > 40,000 patients admitted to an intensive care unit.

Results

We present the FHIR-DHP workflow in respect of transformation of “raw” hospital records into a harmonised, AI-friendly data representation. The pipeline consists of five key preprocessing steps: querying of data from hospital database, FHIR mapping, syntactic validation, transfer of harmonised data into the patient-model database and export of data in an AI-friendly format for further medical applications. A detailed example of FHIR-DHP execution was presented for clinical diagnoses records.

Conclusions

Our approach enables scalable and needs-driven data modelling of large and heterogenous clinical data sets. The FHIR-DHP is a pivotal step towards increasing cooperation, interoperability and quality of patient care in the clinical routine and for medical research.
Requirements to minimize airborne infections related to virus aerosol contamination at indoor cultural events
Authors: Salthammer Tunga , Moriske Heinz-Jörn
Published: November 2022

The SARS-CoV-2 pandemic has resulted in many live events being canceled or held without spectator participation. It is therefore necessary to develop strategies to determine the conditions under which cultural activities can be maintained. In this study the results from available literature were combined with findings, guidelines and regulations for other indoor environments and recommendations were derived. In the cultural sector, the number of experimental investigations, surveys and simulations is comparatively small. This is probably due to the complexity of the events in terms of location and visitor flow, so the respective conditions under which they take place can be very different. It is therefore practically impossible to predict the risk of infection for a specific situation with potential virus spreaders attending or to derive general rules that go beyond the known measures of vaccination, testing, masks and distance. Cultural events can be held under pandemic conditions, provided certain conditions are met. Most study results agree on this. However, any recommendations for hygiene, safety and ventilation measures in cultural institutions can only minimize the risk of infection, but cannot completely rule it out. It is also of considerable importance that visitors protect themselves individually and act responsibly.

Graphical Abstract
Efficacy of a Filtered Far-UVC Handheld Disinfection Device on Reducing Microbial Bioburden of Hospital Surfaces
Authors: Navarathna Thanuri , Jinadatha Chetan , Corona Brandon A. , Coppin John David , Choi Hosoon , Bennett Morgan R. , Ghamande Gautam S. , Williams Marjory D. , Keene Robin E. , Chatterjee Piyali
Published: November 2022

Objectives

The Filtered Far-UVC (FFUV) handheld disinfection device is a small portable device that emits far UVC at 222nm. The objective of this study was to evaluate the device’s ability to kill microbial pathogens on hospital surfaces and compare it to manual disinfection using germicidal sodium hypochlorite wipes.

Methods

A total of 344 observations (4 observations from 86 objects’ surfaces) were sampled with 2 paired samples per surface: a pre- and a post-sodium hypochlorite, and a pre- and a post-FFUV samples. The results were analyzed via a Bayesian multilevel negative binomial regression model. Additionally, the bacterial flora recovered were identified using mass spectrometry.

Results

The estimated mean colony counts for the sodium hypochlorite control and treatment groups were 20.5 (11.7 – 36.0) and 0.1 (0.0 – 0.2) colony forming units (CFUs) respectively. The FFUV control and treatment groups had mean colony counts of 22.2 (12.5 – 40.1) and 4.1 (2.3 – 7.2) CFUs. The sodium hypochlorite samples had an estimated 99.4% (99.0% – 99.7%) reduction in colony counts, while those from the FFUV group had an 81.4% (76.2% − 85.7%) reduction.

Conclusions

Our study demonstrated that FFUV handheld device effectively reduced microbial bioburden on surfaces in the healthcare setting. Several healthcare-associated infections (HAIs) causing pathogens (gram positive and negative bacteria) were retrieved from the pre-clean surfaces. The major benefit of FFUV is likely seen when manual disinfection is not possible or when supplementing cleaners or disinfectants with the low-level disinfection properties.
A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling
Authors: Hackney Jason A. , Shivram Haridha , Heiden Jason Vander , Overall Chris , Orozco Luz , Gao Xia , West Nathan , Qamra Aditi , Chang Diana , Chakrabarti Arindam , Choy David F. , Combes Alexis J. , Courau Tristan , Fragiadakis Gabriela K. , Rao Arjun Arkal , Ray Arja , Tsui Jessica , Hu Kenneth , Kuhn Nicholas F. , Krummel Matthew F. , Erle David J. , Kangelaris Kirsten , Sarma Aartik , Lyon Zoe , Calfee Carolyn S. , Woodruff Prescott G. , Ghale Rajani , Mick Eran , Byrne Ashley , Zha Beth Shoshana , Langelier Charles , Hendrickson Carolyn M. , van der Wijst Monique G.P. , Hartoularos George C. , Grant Tianna , Bueno Raymund , Lee David S. , Greenland John R. , Sun Yang , Perez Richard , Ogorodnikov Anton , Ward Alyssa , Ye Chun Jimmie ,   UCSF COMET Consortium, Ramalingam Thiru , McBride Jacqueline M. , Cai Fang , Teterina Anastasia , Bao Min , Tsai Larry , Rosas Ivan O. , Regev Aviv , Kapadia Sharookh B. , Bauer Rebecca N. , Rosenberger Carrie M.
Published: November 2022

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections, including SARS-CoV-2. Here, we identified a gene program, defined by correlation with EN-RAGE (S100A12) gene expression, which was up-regulated in patient airway and blood myeloid cells. The EN-RAGE program was expressed in 7 cohorts and observed in patients with both COVID-19 and acute respiratory distress syndrome (ARDS) from other causes. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE+myeloid cells express features consistent with suppressor cell functionality, with low HLA-DR and high PD-L1 surface expression and higher expression of T cell-suppressive genes. Sustained EN-RAGE signature expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers, such as PD-1. IL-6 upregulated many of the severity-associated genes in the EN-RAGE gene programin vitro, along with potential mediators of T cell suppression, such as IL-10. Blockade of IL-6 signaling by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of ENRAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.
Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients
Authors: Ramos-Benitez Marcos J. , Strich Jeffrey R. , Alehashemi Sara , Stein Sydney , Rastegar Andre , de Jesus Adriana Almeida , Bhuyan Farzana , Ramelli Sabrina , Babyak Ashley , Perez-Valencia Luis , Vannella Kevin M. , Grubbs Gabrielle , Khurana Surender , Gross Robin , Hadley Kyra , Liang Janie , Mazur Steven , Postnikova Elena , Warner Seth , Holbrook Michael R. , Busch Lindsay M. , Warner Blake , Applefeld Willard , Warner Sarah , Kadri Sameer S , Davey Richard T , Goldbach-Mansky Raphaela , Chertow Daniel S.
Published: November 2022

Understanding early innate immune responses to coronavirus disease 2019 (COVID–19) is crucial to developing targeted therapies to mitigate disease severity. Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection elicits interferon expression leading to transcription of IFN-stimulated genes (ISGs) to control viral replication and spread. SARS-CoV-2 infection also elicits NF-κB signaling which regulates inflammatory cytokine expression contributing to viral control and likely disease severity. Few studies have simultaneously characterized these two components of innate immunity to COVID-19. We designed a study to characterize the expression of interferon alpha-2 (IFNA2) and interferon beta-1 (IFNB1), both type-1 interferons (IFN-1), interferongamma (IFNG), a type-2 interferon (IFN-2), ISGs, and NF-κB response genes in the upper respiratory tract (URT) of patients with mild (outpatient) versus severe (hospitalized) COVID-19. Further, we characterized the weekly dynamics of these responses in the upper and lower respiratory tracts (LRTs) and blood of severe patients to evaluate for compartmental differences. We observed significantly increased ISG and NF-κB responses in the URT of mild compared with severe patients early during illness. This pattern was associated with increasedIFNA2andIFNGexpression in the URT of mild patients, a trend toward increasedIFNB1-expression and significantly increasedSTING/IRF3/cGAS expression in the URT of severe patients. Our by-week across-compartment analysis in severe patients revealed significantly higher ISG responses in the blood compared with the URT and LRT of these patients during the first week of illness, despite significantly lower expression ofIFNA2, IFNB1, andIFNGin blood. NF-κB responses, however, were significantly elevated in the LRT compared with the URT and blood of severe patients during peak illness (week 2). Our data support that severe COVID-19 is associated with impaired interferon signaling in the URT during early illness and robust pro-inflammatory responses in the LRT during peak illness.
Bioinformatic approaches to draft the viral genome sequence of Canary Islands cases related to the multi-country Monkeypox virus 2022-outbreak
Authors: Muñoz-Barrera Adrián , Ciuffreda Laura , Alcoba-Florez Julia , Rubio-Rodríguez Luis A. , Rodríguez-Pérez Héctor , Gil-Campesino Helena , de Artola Diego García-Martínez , Salas-Hernández Josmar , Rodríguez-Núñez Julia , Íñigo-Campos Antonio , Díez-Gil Oscar , González-Montelongo Rafaela , Valenzuela-Fernández Agustín , Lorenzo-Salazar José M. , Flores Carlos
Published: November 2022

During May 2022, the World Health Organization declared community transmission of monkeypox (MPXV) due to a multi-country outbreak. In Europe, several cases of this outbreak were detected in the Canary Islands (Spain). Here we describe the combination of DNA sequencing and bioinformatic approaches, including methods forde novogenome assembly and short- and long-read technologies, used to reconstruct the first MPXV genome isolated in the Canary Islands on the 31stof May 2022 from a male adult patient with mild symptoms. We obtained the best results using a reference-based approach with short reads, evidencing 46-67 nucleotide variants against sequences from the 2018-2019 outbreak, and placing the sequence in the B.1 clade. This study demonstrates the potential of metagenomics sequencing for rapid and precise pathogen identification.
Arrayed Imaging Reflectometry monitoring of anti-viral antibody production throughout vaccination and breakthrough Covid-19
Authors: Klose Alanna M. , Kosoy Gabrielle , Miller Benjamin L.
Published: November 2022

Immune responses to COVID-19 infection and vaccination are individual and varied. There is a need to understand the timeline of vaccination efficacy against current and yet to be discovered viral mutations. Assessing immunity to SARS-CoV-2 in the context of immunity to other respiratory viruses is also valuable. Here we demonstrate the capability of a fully automated prototype Arrayed Imaging Reflectometry (AIR) system to perform reliable longitudinal serology against a 34-plex respiratory array. The array contains antigens for respiratory syncytial virus, seasonal influenza, common human coronaviruses, MERS, SARS-CoV-1, and SARS-CoV-2. AIR measures a change in reflectivity due to the binding of serum antibodies to the antigens on the array. Samples were collected from convalescent COVID-19 donors and individuals vaccinated with a two-dose mRNA vaccine regimen. Vaccinated samples were collected prior to the first dose, one week after the first dose, one week after the second dose, and monthly thereafter. Information following booster dose and/or breakthrough infection is included for a subset of subjects. Longitudinal samples of vaccinated individuals demonstrate a rise and fall of SARS-CoV-2 spike antibodies in agreement with general knowledge of the adaptive immune response and other studies. Linear Regression analysis was performed to understand the relationship between antibodies binding to different antigens on the array. Our analysis identified strong correlations between closely related influenza virus strains as well as correlations between SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. A small test of using diluted whole blood from a fingerstick provided clean arrays with antibody binding comparable to serum. Potential applications include assessing immunity in the context of exposure to multiple respiratory viruses, clinical serology, population monitoring to facilitate public health recommendations, and vaccine development against new viruses and virus mutations.
Identification of multi-omic biomarkers from Fecal DNA for improved Detection of Colorectal Cancer and precancerous lesions
Authors: Fang Yujing , Peng Jiaxi , Li Zhilong , Jiang Ruijingfang , Lin Yuxiang , Shi Ying , Sun Jianlong , Zhuo Duan , Ou Qingjian , Chen Jiali , Wang Xiaohan , Cai Jielun , Zhu Shida , Wan Desen , Wang Yuying , Lu Zhenhai
Published: November 2022

Background

Timely diagnosis and intervention of colorectal cancer (CRC) at curable stages is essential for improving patient survival. Stool samples carry exfoliation of intestinal epithelium, therefore providing excellent opportunity for non-invasive diagnosis of CRC as well as precancerous lesions. In this study, we aimed to conduct multi-dimensional analysis of fecal DNA and investigate the utility of different types of biomarkers for CRC detection.

Method

In this case-control study, we performed comprehensive analyses of the genomic, epigenomic, and metagenomic features of fecal DNA from CRC patients, individuals with advanced precancerous lesions (APLs) and controls. DNA methylation markers were identified by whole genome bisulfite sequencing of paired colorectal cancer and normal tissues. A multi-gene fecal DNA methylation test was then developed based on three marker genes (SDC2, ADHFE1andPPP2R5C) using quantitative methylation-specific PCR (qMSP), and validated on fecal DNA samples. Genomic mutation profiles as well as microbiome signatures of fecal DNA were analyzed using high-throughput sequencing.

Results

The methylation-based fecal DNA test demonstrated an overall sensitivity of 88% for CRC and 46.2% for APL respectively, and a specificity of 91.8% for controls. On the other hand, the mutation-based diagnostic model yielded limited sensitivity, and combined detection of methylation markers and mutation in fecal DNA did not improve the assay performance. Meanwhile, a diagnostic model based on the relative abundance of bacterial species showed inferior performance than the methylation-based model. Finally, integrated diagnostic model combining both methylation and microbial markers showed an enhanced performance (AUC= 0.95) compared to methylation markers alone.

Conclusions

The multi-gene fecal DNA methylation test provided remarkable diagnostic performance for CRCs and APLs. Furthermore, multi-target assay integrating both methylation and microbial markers may further improve the diagnostic performance. Our findings may aid in the development of novel diagnostic tools for CRC.
Exposure profiles in pregnant women from a birth cohort in a highly contaminated area of southern Italy
Authors: Drago Gaspare , Ruggieri Silvia , Sprovieri Mario , Rizzo Giulia , Colombo Paolo , Giosuè Cristina , Quinci Enza , Traina Anna , Gastaldelli Amalia , Cibella Fabio , Panunzi Simona
Published: November 2022

Protecting the health of pregnant women from environmental stressors is crucial for reducing the burden of non-communicable diseases. In industrially contaminated sites, this action is particularly challenging due to the heterogeneous pollutant mixtures in environmental matrices. Aim of this study was to evaluate distribution patterns of mercury, hexacholobenzene and polychlorobyfenils in the serum of 161 pregnant women recruited in the framework of the NEHO cohort and living both inside and outside the National Priority Contaminated Site (NPCS) of Priolo. Food macro-categories were determined, and serum levels of contaminants were used to perform k-means cluster analysis and identify the role of food in pollutant transfer from the environment. Two groups of mothers with high and low measured pollutant levels were distinguished. Concentrations in mothers in the high-exposure cluster were at least twofold for all the evaluated pollutants (p<0.0001) and includes mothers living inside and outside NPCS, with predominance of individuals from the NPCS (p=0.045). Fish and vegetable consumption was higher in the high-exposure cluster (p=0.02). These findings suggest a direct link between marine sediments and soil contaminations, which in turn drives maternal exposure through the food chain. Such consideration appears poorly investigated in the context of contaminated sites.

Highlights

- HCB, PCBs and Hg were measured in pregnant women from a highly contaminated area

- Pregnant women’s exposure profiles were obtained through k-means cluster analysis

- Distance of residence from emission sources only partially explains exposure levels

- Maternal age and food consumption appear to primarily drive contaminant levels

Abstract Figure
Association of Gout with Brain Reserve and Vulnerability to Neurodegenerative Disease
Authors: Topiwala Anya , Mankia Kulveer , Bell Steven , Webb Alastair , Ebmeier Klaus P , Howard Isobel , Wang Chaoyue , Alfaro-Almagro Fidel , Miller Karla , Burgess Stephen , Smith Stephen , Nichols Thomas E
Published: November 2022

Objectiv

To assess the associations between gout, brain structure, and neurodegenerative disease incidence.

Methods

Using observational and Mendelian randomization analyses we investigated causal relationships between gout and brain health. Exposures included gout diagnosis (from self-report, linked health records and death records) and genetically proxied gout and serum urate. Outcomes were neuroimaging markers of brain structure and neurodegenerative disease incidence (ascertained through self-report, health records and death reports). Cox proportional hazards models were used to examine time to neurodegenerative disease diagnosis.

Results

11,735 UK Biobank participants (mean age 55.5±8.0 years and 50.5% female) had a diagnosis of gout (n=1165 in MRI subset). Dementia was ascertained in 3126 individuals over a mean follow-up time of 12.4±1.9 years. Gout patients had smaller global and regional brain volumes and higher brain iron markers. Genetic associations mirrored observational associations. Genetically proxied gout associated with lower global grey matter volume (beta= -0.05[-0.08 to -0.01]). Participants with gout had higher incidence of all-cause dementia (hazard ratio (HR)=1.60, 95% confidence interval (CI) [1.38-1.85]), Parkinson’s disease (HR=1.43[1.15 to 1.79]), and probable essential tremor (HR=6.75[5.69 to 8.00]). Risks were strongly time dependent, whereby associations with incident dementia were highest in the first 3 years after gout diagnosis (HR=7.40[4.95 to 11.07]).

Conclusions

These findings suggest gout is causally related to several measures of brain structure. Lower brain reserve amongst gout patients may explain their higher vulnerability to multiple neurodegenerative diseases.

Key points

What is already known on this topic?

Studies of neurodegenerative disease risk in gout are contradictory.

Relationships with neuroimaging markers of brain structure, which may offer insights, are uncertain.

What this study adds?

In this prospective cohort study gout was associated with smaller brain volumes and higher incidence of multiple neurodegenerative diseases.

Mendelian randomization analyses suggested gout is causally related to brain structure.

How might this study affect research, practice or policy?

Our findings emphasise the importance for clinicians of assessing for motor and cognitive impairments amongst gout patients, particularly in early years after diagnosis.
Patterns of West Nile virus in the Northeastern United States using negative binomial and mechanistic trait-based models
Authors: Keyel Alexander C.
Published: November 2022

West Nile virus primarily infects birds and mosquitoes but has also caused over 2000 human deaths, and >50,000 reported human cases. Present-day West Nile virus risk was described for the Northeastern United States, using a negative binomial model. Changes in risk due to climate change were examined for the next decade using a temperature-trait model. West Nile virus risk was generally expected to increase over the next decade due to changes in temperature, but the changes in risk were generally small. Many, but not all, populous counties in the northeast are already near peak risk. Several years in a row of low case numbers is consistent with a negative binomial, and should not be interpreted as a change in disease dynamics. Public health budgets need to be prepared for the expected infrequent years with higher-than-average cases. Absence of reported cases from low-population counties is consistent with similar risk as nearby counties with cases.
Using species richness calculations to model the global profile of unsampled pathogenic variants: Examples fromBRCA1andBRCA2
Authors: Rao Nandana D. , Shirts Brian H.
Published: November 2022

There have been many surveys of genetic variation inBRCA1andBRCA2to identify variant prevalence and catalogue population specific variants, yet none have evaluated the magnitude of unobserved variation. We applied species richness estimation methods from ecology to estimate “variant richness” and determine how many germline pathogenicBRCA1/2variants have yet to be identified and the frequency of these missing variants in different populations. We also estimated the prevalence of germline pathogenicBRCA1/2variants and identified those expected to be most common. Data was obtained from a literature search including studies conducted globally that tested the entirety ofBRCA1/2for pathogenic variation. Across countries, 45% to 88% of variants were estimated to be missing, i.e., present in the population but not observed in study data. Estimated variant frequencies in each country showed a higher proportion of rare variants compared to recurrent variants. The median prevalence estimate ofBRCA1/2pathogenic variant carriers was 0.64%.BRCA1c.68_69del is likely the most recurrentBRCA1/2variant globally due to its estimated prevalence in India. Modeling variant richness using ecology methods may assist in evaluating clinical targeted assays by providing a picture of what is observed with estimates of what is still unknown.
Glucocorticoid-regulated bidirectional enhancer RNA transcription pinpoints functional genetic variants linked to asthma
Authors: Sasse Sarah K. , Dahlin Amber , Sanford Lynn , Gruca Margaret A. , Gupta Arnav , Gally Fabienne , Wu Ann Chen , Iribarren Carlos , Dowell Robin D. , Weiss Scott T. , Gerber Anthony N.
Published: November 2022

Genome-wide association studies of asthma have not explained environmental risk or variable clinical efficacy of glucocorticoids. Bidirectional enhancer RNA (eRNA) transcription is a widespread response to environmental signals and glucocorticoids. Therefore, we investigated whether single nucleotide polymorphisms (SNPs) within dynamically regulated eRNA-transcribing regions contribute to genetic variation in asthma. Through applying multivariate regression modeling with permutation-based significance thresholding to a large clinical cohort, we identified novel associations between asthma and 35 SNPs located in eRNA-transcribing regions implicated in regulating diverse cellular processes relevant to asthma. Functional validation established thatrs258760(mean allele frequency = 0.34, asthma odds ratio = 0.95; P = 5.04E-03) eliminates an active aryl hydrocarbon receptor (AHR) response element linked to transcriptional regulation of the glucocorticoid receptor gene by AHR ligands commonly found in air pollution. Our findings establish eRNA signatures as a tool for discovery of functional genetic variants and define a novel link between air pollution, glucocorticoid signaling and asthma.
Altered Resting-State Functional Connectivity in the Anterior Versus Posterior Hippocampus in Post-traumatic Stress Disorder: The Central Role of the Anterior Hippocampus
Authors: Chaposhloo Mohammad , Nicholson Andrew A. , Becker Suzanna , McKinnon Margaret C. , Lanius Ruth , Shaw Saurabh Bhaskar ,   Alzheimer’s Disease Neuroimaging Initiative
Published: November 2022

Background

Post-traumatic stress disorder can be viewed as a memory disorder, with trauma-related flashbacks being a core symptom. Given the central role of the hippocampus in autobiographical memory, surprisingly, there is mixed evidence concerning altered hippocampal functional connectivity in PTSD. We shed light on this discrepancy by considering the distinct roles of the anterior versus posterior hippocampus and examine how this distinction may map onto whole-brain resting-state functional connectivity patterns among those with and without PTSD.

Methods

We first assessed whole-brain between-group differences in the functional connectivity profiles of the anterior and posterior hippocampus within a publicly available data set of resting-state fMRI data fromn=31 male Vietnam War veterans diagnosed with PTSD andn=29 age-matched combat-exposed male controls. Next, the connectivity patterns of each subject within the PTSD group were correlated with their PTSD symptom scores. Finally, the between-group differences in whole-brain functional connectivity profiles discovered for the anterior and posterior hippocampal seeds were used to prescribe post-hoc ROIs, which were then used to perform ROI-to-ROI functional connectivity and graph-theoretic analyses.

Results

The PTSD group showed increased functional connectivity of the anterior hippocampus with affective brain regions (anterior/posterior insula, orbitofrontal cortex, temporal pole) and decreased functional connectivity of the anterior/posterior hippocampus with regions involved in processing bodily selfconsciousness (supramarginal gyrus). Notably, decreased anterior hippocampus connectivity with the posterior cingulate cortex /precuneus was associated with increased PTSD symptom severity. The left anterior hippocampus also emerged as a central locus of abnormal functional connectivity, with graph-theoretic measures suggestive of a more central hub-like role in those with PTSD compared to trauma-exposed controls.

Conclusions

Our results highlight that the anterior hippocampus plays a critical role in the neurocircuitry underlying PTSD and underscore the importance of the differential roles of hippocampal sub-regions in serving as biomarkers of PTSD.