bluuebunny/crossref_metadata_2025_split huggingface dataset:
The latitude gradient for multiple sclerosis prevalence is established in the early life course
Authors: Sabel Clive E , Pearson John F , Mason Deborah F , Willoughby Ernest , Abernethy David A , Taylor Bruce V 
Published: March 2021

Abstract
The strongest epidemiological clue that the environment at the population level has a significant impact on the risk of developing multiple sclerosis is the well established, and in many instances, increasing latitudinal gradient of prevalence, incidence and mortality globally, with prevalence increasing by up to 10-fold between the equator and 60° north and south. The drivers of this gradient are thought to be environmental with latitude seen as a proxy for ultraviolet radiation and thus vitamin D production; however, other factors may also play a role. Several important questions remain unanswered, particularly when in the life course is the gradient established, does lifetime migration mitigate or exacerbate previously reported latitude gradients at location of diagnosis, and do factors such as sex or multiple sclerosis disease phenotype influence the timing or significance of the gradient? Utilizing lifetime residence calendars collected as part of the New Zealand National Multiple Sclerosis Prevalence Study, we constructed lifetime latitudinal gradients for multiple sclerosis from birth to prevalence day in 2006 taking into account migration internally and externally and then analysed by sex and multiple sclerosis clinical course phenotype. Of 2917 individuals living in New Zealand on prevalence day, 7 March 2006, with multiple sclerosis, 2127 completed the life course questionnaire and of these, 1587 were born in New Zealand. All cohorts and sub-cohorts were representative of the overall multiple sclerosis population in New Zealand on prevalence day. We found that the prevalence gradient was present at birth and was, in fact, stronger than at census day, and the slope of the gradient persisted until the age of 12 before gradually declining. We found that internal and external migration into New Zealand had little, if any, effect on the gradient except to decrease the significance of the gradient somewhat. Finally, we found as we had reported previously, that the lifetime prevalence gradients were largely driven by females with relapse onset multiple sclerosis. These findings confirm for the first time the importance of early life environmental exposures in the risk of multiple sclerosis indicating strongly that exposures as early as in utero and at birth drive the latitudinal gradient. Consequently, prevention studies should be focused on high-risk individuals and populations from the earliest possible time points especially, when appropriate, on females.
Human cardiosphere-derived stromal cells exposed to SARS-CoV-2 evolve into hyper-inflammatory/pro-fibrotic phenotype and produce infective viral particles depending on the levels of ACE2 receptor expression
Authors: Amendola Alessandra , Garoffolo Gloria , Songia Paola , Nardacci Roberta , Ferrari Silvia , Bernava Giacomo , Canzano Paola , Myasoedova Veronika , Colavita Francesca , Castilletti Concetta , Sberna Giuseppe , Capobianchi Maria Rosaria , Piacentini Mauro , Agrifoglio Marco , Colombo Gualtiero Ivanoe , Poggio Paolo , Pesce Maurizio 
Published: March 2021

Abstract

Aims
Patients with severe respiratory syndrome caused by SARS-CoV-2 undergo cardiac complications due to hyper-inflammatory conditions. Although the presence of the virus has been detected in the myocardium of infected patients, and infection of induced pluripotent cell-derived cardiomyocytes has been demonstrated, the reported expression of Angiotensin-Converting Enzyme-2 (ACE2) in cardiac stromal cells suggests that SARS-CoV-2 may determine cardiac injury by sustaining productive infection and increasing inflammation.

Methods and results
We analysed expression of ACE2 receptor in primary human cardiac stromal cells derived from cardiospheres, using proteomics and transcriptomics before exposing them to SARS-CoV-2 in vitro. Using conventional and high sensitivity PCR methods, we measured virus release in the cellular supernatants and monitored the intracellular viral bioprocessing. We performed high-resolution imaging to show the sites of intracellular viral production and demonstrated the presence of viral particles in the cells with electron microscopy. We finally used RT–qPCR assays to detect genes linked to innate immunity and fibrotic pathways coherently regulated in cells after exposure to the virus.

Conclusions
Our findings indicate that cardiac stromal cells are susceptible to SARS-CoV-2 infection and produce variable viral yields depending on the extent of cellular ACE2 receptor expression. Interestingly, these cells also evolved towards hyper-inflammatory/pro-fibrotic phenotypes independently of ACE2 levels. Thus, SARS-CoV-2 infection of myocardial stromal cells could be involved in cardiac injury and explain the high number of complications observed in severe cases of COVID-19.
European-wide policymaking at the urban level: a qualitative study
Authors: Mueller Julia , Patterson Lesley , Jakab Matyas , Higgerson James , Steels Stephanie , Verma Arpana 
Published: March 2021

Abstract

Background
Inter-urban area (UA) health inequalities can be as dramatic as those between high and low-income countries. Policies need to focus on the determinants of health specific to UAs to effect change. This study therefore aimed to determine the degree to which policymakers from different countries could make autonomous health and wellbeing policy decisions for their urban jurisdiction area.

Methods
We conducted a cross-sectional, qualitative interview study with policymakers recruited from eight European countries (N = 37).

Results
The reported autonomy among policymakers varied considerably between countries, from little or no autonomy and strict adherence to national directives (e.g. Slovak Republic) to a high degree of autonomy and ability to interpret national guidelines to local context (e.g. Norway). The main perceived barriers to implementation of local policies were political, and the importance of regular and effective communication with stakeholders, especially politicians, was emphasized. Having qualified health professionals in positions of influence within the UA was cited as a strong driver of the public health (PH) agenda at the UA level.

Conclusion
Local-level policy development and implementation depends strongly on the degree of autonomy and independence of policymakers, which in turn depends on the organization, structure and financial budget allocation of PH services. While high levels of centralization in small, relatively homogenous countries may enhance efficient use of resources, larger, more diverse countries may benefit from devolution to smaller geographical regions.
Gag p24 Is a Marker of Human Immunodeficiency Virus Expression in Tissues and Correlates With Immune Response
Authors: Wu Guoxin , Zuck Paul , Goh Shih Lin , Milush Jeffrey M , Vohra Poonam , Wong Joseph K , Somsouk Ma , Yukl Steven A , Shacklett Barbara L , Chomont Nicolas , Haase Ashley T , Hatano Hiroyu , Schacker Timothy W , Deeks Steven G , Hazuda Daria J , Hunt Peter W , Howell Bonnie J 
Published: March 2021

Abstract
We demonstrate that human immunodeficiency virus (HIV) gag p24 protein is more readily detected in gut and lymph node tissues than in blood CD4+ T cells and correlates better with CD4 count during antiretroviral therapy (ART). Gut p24 levels also measurably decline with ART in natural controllers. During ART, gut p24 expression is more strongly associated both with HIV-specific CD8+ T-cell frequency and plasma soluble CD14 levels than gut HIV RNA expression. This study supports using gag p24 as a marker of HIV expression in HIV+ tissues to study effects of viral persistence and to monitor efficacy of treatment in HIV-based clearance studies.
Recommendations for Influenza Vaccination in Burns Patients Based on a Systematic Review of the Evidence
Authors: Nweze Kirsty , Hart-Pinto Andrew , Philip Liby , Mortimer Kalani , Whitehead Kathryn A , Shokrollahi Kayvan 
Published: March 2021

Abstract
Severe burn injury is a serious systemic insult that can lead to life-threatening secondary infections. Immunosuppression, inhalation injury, and prolonged length of hospital stay are factors that predispose patients to severe respiratory tract infections. Furthermore, evidence shows that burns can put one at risk of infection long after the original injury. Currently in the United Kingdom, the annual National Flu Immunisation programme outlines guidance for groups who are deemed high risk and, therefore, eligible for the influenza vaccine. At present, no guidance exists for the administration of the influenza vaccine in burn-injured patients, despite knowledge of immunosuppression. The aim of this literature review is to examine the evidence for associations between burn injury and influenza and, where available, evaluate efficacy of influenza vaccines in this cohort. In addition, literature was searched for the effectiveness of the influenza vaccine in patients 65 years and above and in patients admitted to the intensive care unit (ICU), two domains common to patients with severe burns. Three papers were found to suggest increased susceptibility to influenza following burn injury; however, no papers studying the effectiveness of the influenza vaccine in this group were found. Several studies demonstrated improved outcomes in patients over 65 years and patients admitted to ICU. Following the evaluation of the evidence, this review advocates for the consideration of hospitalized burn patients for the influenza vaccine. We suggest the avoidance of vaccine administration in the acute burn phase. Further prospective clinical trials would be required to validate these findings.
Factors Associated With Mortality Following Burns Complicated by Necrotizing Skin and Soft Tissue Infections: A Systematic Review and Meta-Analysis of Individual Participant Data
Authors: Klifto Kevin M , Gurno Caresse F , Seal Stella M , Hultman C Scott 
Published: March 2021

Abstract
We reviewed studies with individual participant data of patients who sustained burn injury and subsequently developed necrotizing skin and soft tissue infections (NSTI). Characteristics and managements were compared between patients who lived and patients who died to determine factors associated with mortality. Six databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, and CINAHL) were searched. PRISMA-IPD guidelines were followed throughout the review. Eligible patients sustained a burn injury, treated in any setting, and diagnosed with a NSTI following burn injury. Comparisons were made between burned patients who lived “non-mortality” and burned patients who died “mortality” following NSTI using non-parametric univariate analyses. Fifty-eight studies with 78 patients were published from 1970 through 2019. Non-mortality resulted in 58 patients and mortality resulted in 20 patients. Patients with mortality had significantly greater median %TBSA burned (45%[IQR:44–64%] vs 35%[IQR:11–59%], P = .033), more intubations (79% vs 43%, P = .013), less debridements (83% vs 98%, P = .039), less skin excisions (83% vs 98%, P = .039), more complications (100% vs 50%, P &lt; .001), management at a burn center (100% vs 71%, P = .008), underwent less flap surgeries (5% vs 35%, P = .014), less graft survival (25% vs 86%, P &lt; .001), and less healed wounds (5% vs 95%, P &lt; .001), compared to patients with non-mortality, respectively. Non-mortality patients had more debridements, skin excised, systemic antimicrobials, skin graft survival, flaps, improvement following surgery, and healed wounds compared to mortality patients. Mortality patients had greater %TBSA burned, intubations, management at a burn center and complications compared to non-mortality patients.
Association Between Sex and Immune-Related Adverse Events During Immune Checkpoint Inhibitor Therapy
Authors: Jing Ying , Zhang Yongchang , Wang Jing , Li Kunyan , Chen Xue , Heng Jianfu , Gao Qian , Ye Youqiong , Zhang Zhao , Liu Yaoming , Lou Yanyan , Lin Steven H , Diao Lixia , Liu Hong , Chen Xiang , Mills Gordon B , Han Leng 
Published: March 2021

Abstract

Background
Accumulated evidence supports the existence of sex-associated differences in immune systems. Understanding the role of sex in immune-related adverse events (irAEs) is important for management of irAE in patients receiving immunotherapy.

Methods
We performed meta-analysis on published clinical study data and multivariable logistic regression on pharmacovigilance data and applied a propensity algorithm to The Cancer Genome Atlas omics data. We further validated our observations in 2 independent in-house cohorts of 179 and 767 cancer patients treated with immune checkpoint inhibitors.

Results
A meta-analysis using 13 clinical studies that reported on 1096 female patients (36.8%, 95% confidence interval [CI] = 35.0% to 38.5%) and 1886 male patients (63.2%, 95% CI = 61.5% to 65.0%) demonstrated no statistically significant irAE risk difference between the sexes (odds ratio [OR] = 1.19, 95% CI = 0.91 to 1.54, 2-sided P = .21). Multivariable logistic regression analysis of 12 225 patients from the Food and drug administration Adverse Event Reporting System (FAERS) and 10 979 patients from VigiBase showed no statistically significant difference in irAEs by sex. A propensity score algorithm used on multi-omics data for 6019 patients from The Cancer Genome Atlas found no statistically significant difference by sex for irAE-related factors or pathways. The retrospective analysis of 2 in-house patient cohorts validated these results (OR = 1.55, 95% CI = 0.98 to 2.47, false discovery rate = 0.13, for cohort 1; OR = 1.16, 95% CI = 0.86 to 1.57, false discovery rate = 0.39, for cohort 2).

Conclusions
We observed minimal sex-associated differences in irAEs among cancer patients who received immune checkpoint inhibitor therapy. It may be unnecessary to consider sex effects for irAE management in clinical practice.
Multicolour photometry and Gaia EDR3 astrometry of two couples of binary clusters (NGC 5617 and Trumpler 22) and (NGC 3293 and NGC 3324)
Authors: Bisht D , Zhu Qingfeng , Yadav R K S , Ganesh Shashikiran , Rangwal Geeta , Durgapal Alok , Sariya Devesh P , Jiang Ing-Guey 
Published: March 2021

ABSTRACT
This paper presents a comprehensive analysis of two pairs of binary clusters (NGC 5617 and Trumpler 22) and (NGC 3293 and NGC 3324) located in the fourth quadrant of our Galaxy. For this purpose, we use different data taken from VVV survey, WISE, VPHAS, APASS, and GLIMPSE along with Gaia EDR3 astrometric data. We identified 584, 429, 692, and 273 most probable cluster members with membership probability higher than $80 {{\ \rm per\ cent}}$ towards the region of the clusters NGC 5617, Trumpler 22, NGC 3293, and NGC 3324. We estimated the value of $R=\frac{A_{V}}{E(B-V)}$ as ∼3.1 for the clusters NGC 5617 and Trumpler 22, which indicates the normal extinction law. The values of $R\, \sim 3.8$ and ∼1.9 represent the abnormal extinction law towards the clusters NGC 3293 and NGC 3324. Our kinematical analysis shows that all these clusters have circular orbits. Ages are found to be 90 ± 10 and 12 ± 3 Myr for the cluster pairs (NGC 5617 and Trumpler 22) and (NGC 3293 and NGC 3324), respectively. The distances of 2.43 ± 0.08, 2.64 ± 0.07, 2.59 ± 0.1, and 2.80 ± 0.2 kpc estimated using parallax are consistent with the values calculated by using the distance modulus. We have also identified 18 and 44 young stellar object candidates present in NGC 5617 and Trumpler 22, respectively. Mass function slopes are found to be in fair agreement with the Salpeter’s value. The dynamical study of these objects shows a lack of faint stars in their inner regions, which leads to the mass-segregation effect. Our study indicates that NGC 5617 and Trumpler 22 are dynamically relaxed but the other pair of clusters are not. Orbital along with the physical parameters show that the clusters in both pairs are physically connected.
Formation of Al containing molecular complexes in the gas phase in dense molecular clouds: quantum study of the radiative association of Al++H2 and Al++D2
Authors: Jones (nee Burdakova) Daria , Nyman Gunnar , Stoecklin Thierry 
Published: March 2021

ABSTRACT
Radiative association (RA) of Al+ with H2 is the first step in the formation of AlH in gas phase and is here investigated theoretically. We use recent potential energy and dipole moment surfaces and a quantum approach based on the driven equations formalism for performing the dynamics for both the Al+-H2 and Al+-D2 systems. The obtained RA rate coefficients are compared with previous evaluations based on transition state theory and found to be orders of magnitude larger. They are also compared to those obtained recently for the similar systems Na+-H2/D2. The possible role played by RA of Al+ with H2 in the gas phase chemistry of dense molecular clouds is discussed.
Lyman-alpha spectroscopy of extreme [O iii] emitting galaxies at z ≃ 2-3: implications for Lyα visibility and LyC leakage at z &gt; 6
Authors: Tang Mengtao , Stark Daniel P , Chevallard Jacopo , Charlot Stéphane , Endsley Ryan , Congiu Enrico 
Published: March 2021

ABSTRACT
Spectroscopic observations of massive z &gt; 7 galaxies selected to have extremely large [O iii] + H β equivalent width (EW ∼1500 Å) have recently revealed large Ly α detection rates, in contrast to the weak emission seen in the general population. Why these systems are uniquely visible in Ly α at redshifts where the intergalactic medium (IGM) is likely significantly neutral is not clear. With the goal of better understanding these results, we have begun a campaign with MMT and Magellan to measure Ly α in galaxies with similar [O iii] + H β EWs at z ≃ 2–3. At these redshifts, the IGM is highly ionized, allowing us to clearly disentangle how the Ly α properties depend on the [O iii] + H β EW. Here, we present Ly α EWs of 49 galaxies at z = 2.2–3.7 with intense [O iii] + H β line emission (EW = 300–3000 Å). Our results demonstrate that strong Ly α emission (EW &gt;20 Å) becomes more common in galaxies with larger [O iii] + H β EW, reflecting a combination of increasingly efficient ionizing photon production and enhanced transmission of Ly α. Among the galaxies with the most extreme [O iii] + H β emission (EW ∼1500 Å), we find that strong Ly α emission is not ubiquitous, with only 50 per cent of our population showing Ly α EW &gt;20 Å. Our data suggest that the range of Ly α strengths is related to the observed ellipticity, with those systems that appear edge-on or elongated having weaker Ly α emission. We use these results to interpret the anomalous Ly α properties seen in z &gt; 7 galaxies with extreme [O iii] + H β emission and discuss implications for the escape of ionizing radiation from these extreme line emitting galaxies.
An ALMA survey of the SCUBA-2 Cosmology Legacy Survey UKIDSS/UDS field: halo masses for submillimetre galaxies
Authors: Stach S M , Smail I , Amvrosiadis A , Swinbank A M , Dudzevičiūtė U , Geach J E , Almaini O , Birkin J E , Chen Chian-Chou , Conselice C J , Cooke E A , Coppin K E K , Dunlop J S , Farrah D , Ikarashi S , Ivison R J , Wardlow J L 
Published: March 2021

ABSTRACT
We present an analysis of the spatial clustering of a large sample of high-resolution, interferometically identified, submillimetre galaxies (SMGs). We measure the projected cross-correlation function of ∼350 SMGs in the UKIDSS Ultra Deep-Survey Field across a redshift range of z = 1.5–3 utilizing a method that incorporates the uncertainties in the redshift measurements for both the SMGs and cross-correlated galaxies through sampling their full probability distribution functions. By measuring the absolute linear bias of the SMGs, we derive halo masses of $\log _{10}(M_{\rm halo}[{h^{-1}\, \rm M_{\odot }}])$ ∼ 12.8 with no evidence of evolution in the halo masses with redshift, contrary to some previous work. From considering models of halo mass growth rates, we predict that the SMGs will reside in haloes of mass $\log _{10}(M_{\rm halo}[{h^{-1}\, \rm M_{\odot }}])$ ∼ 13.2 at z = 0, consistent with the expectation that the majority of z = 1.5–3 SMGs will evolve into present-day spheroidal galaxies. Finally, comparing to models of stellar-to-halo mass ratios, we show that SMGs may correspond to systems that are maximally efficient at converting their gas reservoirs into stars. We compare them to a simple model for gas cooling in haloes that suggests that the unique properties of the SMG population, including their high levels of star formation and their redshift distribution, are a result of the SMGs being the most massive galaxies that are still able to accrete cool gas from their surrounding intragalactic medium.
Osmium–arene complexes with high potency towards Mycobacterium tuberculosis
Authors: Coverdale James P C , Guy Collette S , Bridgewater Hannah E , Needham Russell J , Fullam Elizabeth , Sadler Peter J 
Published: March 2021

Abstract
The treatment of tuberculosis (TB) poses a major challenge as frontline therapeutic agents become increasingly ineffective with the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). To combat this global health problem, new antitubercular agents with novel modes of action are needed. We have screened a close family of 17 organometallic half-sandwich Os(II) complexes [(arene)Os(phenyl-azo/imino-pyridine)(Cl/I)]+Y– containing various arenes (p-cymene, biphenyl, or terphenyl), and NMe2, F, Cl, or Br phenyl or pyridyl substituents, for activity towards Mtb in comparison with normal human lung cells (MRC5). In general, complexes with a monodentate iodido ligand were more potent than chlorido complexes, and the five most potent iodido complexes (MIC 1.25–2.5 µM) have an electron-donating Me2N or OH substituent on the phenyl ring. As expected, the counter anion Y (PF6–, Cl–, I–) had little effect on the activity. The pattern of potency of the complexes towards Mtb is similar to that towards human cells, perhaps because in both cases intracellular thiols are likely to be involved in their activation and their redox mechanism of action. The most active complex against Mtb is the p-cymene Os(II) NMe2-phenyl-azopyridine iodido complex (2), a relatively inert complex that also exhibits potent activity towards cancer cells. The uptake of Os from complex 2 by Mtb is rapid and peaks after 6 h, with temperature-dependence studies suggesting a major role for active transport.
Significance to Metallomics
Antimicrobial resistance is a global health problem. New advances are urgently needed in the discovery of new antibiotics with novel mechanisms of action. Half-sandwich organometallic complexes offer a versatile platform for drug design. We show that with an appropriate choice of the arene, an N,N-chelated ligand, and monodentate ligand, half-sandwich organo–osmium(II) complexes can exhibit potent activity towards Mycobacterium tuberculosis (Mtb), the leading cause of death from a single infectious agent. The patterns of activity of the 17 azo- and imino-pyridine complexes studied here towards Mtb and normal lung cells suggest a common redox mechanism of action involving intracellular thiols.