bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Hearing Impairment With Higher-Level Physical Functioning and Walking Endurance: Results From the Baltimore Longitudinal Study of Aging
Authors: Martinez-Amezcua Pablo , Kuo Pei-Lun , Reed Nicholas S , Simonsick Eleanor M , Agrawal Yuri , Lin Frank R , Deal Jennifer A , Ferrucci Luigi , Schrack Jennifer A
Published: May 2021

Background

Although hearing impairment (HI) is linked to poorer physical functioning, the longitudinal associations between HI and higher-level functional measures are unclear.

Method

Data are from the Baltimore Longitudinal Study of Aging (2012–2019). Using pure-tone audiometry, we categorized hearing into normal, mild, and moderate or greater HI. Physical function was assessed with the expanded Short Physical Performance Battery (eSPPB) and walking endurance with time to walk 400 m. Multivariable and mixed-effects linear models tested the hypotheses that participants with HI, at baseline, have poorer physical performance and walking endurance, and faster decline over time (up to 6 measurements). In a subset (n = 526), we further adjusted for vestibular function. Among participants with HI, we evaluated the differences in eSPPB scores and walking endurance between hearing aid users and nonusers.

Results

Of 831 participants, 26% had mild, and 17% moderate or greater HI. After adjustment for demographics and medical history, moderate or greater impairment versus normal hearing was associated with poorer function (0.17 [95% CI: 0.09, 0.26] lower eSPPB score, and 13.3 [95% CI: 3.31, 23.4] seconds slower 400-m walk time) and faster decline in these parameters over 6 years. Adjustment for vestibular function did not attenuate these associations. Hearing aid users walked 400 m 24 seconds faster than nonusers (p = .001).

Conclusion

Moderate or greater HI is associated with poorer initial and greater decline in higher-level physical performance. The observation that hearing aid users had better walking endurance suggests that screening for and treatment of HI may delay or slow progression of hearing-related functional decline.
Liver health events: an indigenous community-led model to enhance HCV screening and linkage to care
Authors: Pandey Mamata , Konrad Stephanie , Reed Noreen , Ahenakew Vanessa , Isbister Patricia , Isbister Tanys , Gallagher Lesley , Campbell Trisha , Skinner Stuart
Published: May 2021

Despite high prevalence of hepatitis C virus (HCV), linkage to care and treatment for Indigenous people is low. In an Indigenous community in Saskatchewan, Canada a retrospective review identified 200 individuals (∼12% prevalence) had HCV antibodies though majority lacked ribonucleic acid (RNA) testing, and few received treatment despite availability of an effective cure. Following Indigenous oral traditions, focus group discussions were held with key community members and leadership. Participants emphasized the need for a community-based screening and treatment programme. A team of community members, peers and healthcare professionals developed a streamlined screening pathway termed ‘liver health event’ (LHE) to reduce stigma, reach undiagnosed, re-engage previously diagnosed, and ensure rapid linkage to care/treatment. LHEs began December 2016. Statistics were tracked for each event. As of July 2019, there were 10 LHEs with 540 participants, 227 hepatitis C tests and 346 FibroScans completed. This represented 294 unique individuals, of which 64.3% were tested, and of those, 40.8% were Ab positive. Among those positive for antibodies, 41.7% had active hepatitis C infections, and among these, 90% were linked to care, and 14 new positive individuals were identified. Following the success of LHEs, these were adapted and implemented in 10 other communities in this region, resulting in 17 additional LHEs. This intervention is reaching the undiagnosed and linking clients to care through a low-barrier and de-stigmatizing approach. It has facilitated collaboration, knowledge exchange and mentorship between Indigenous communities, significantly impacting health outcomes of Indigenous people in this region.
Practice-guided public health philosophy
Authors: Folker Anna Paldam , Lauridsen Sigurd , Andersen Martin , Kongsholm Nana Cecilie , Varga Somogy
Published: May 2021

Although highly relevant, philosophical theory and philosophical competences are rarely integrated in empirical public health research. We suggest a variant of applied philosophy that is valuable for the development and improvement of public health research. We call it practice-guided public health philosophy because: (i) research questions derive from public health challenges, i.e. real-life concerns that relate to the prevention of disease or the promotion of health and well-being, (ii) the ultimate test of success lies within an empirical framework aiming to improve public health practices and (iii) philosophers collaborate very closely with different kinds of empirical researchers in the different stages of the research process. Using examples from current public health projects at the National Institute of Public Health at the University of Southern Denmark, we outline three paradigmatic cases of practice-guided public health philosophy: (i) by using philosophy as an idea generator of empirical research, (ii) by using philosophy as a frame of reference for interpreting ethnographic data and (iii) by using philosophy as an explanatory resource for discussing survey and register data.
Measured versus predicted postoperative pulmonary function at repeated times up to 1 year after lobectomy
Authors: Shibazaki Takamasa , Mori Shohei , Harada Eriko , Shigemori Rintaro , Kato Daiki , Matsudaira Hideki , Hirano Jun , Ohtsuka Takashi
Published: May 2021

OBJECTIVES

Postoperative pulmonary function is difficult to predict accurately, because it changes from the time of the operation and is also affected by various factors. The objective of this study was to assess the accuracy of predicted postoperative forced expiratory volume in 1 s (FEV1) at different postoperative times after lobectomy.

METHODS

This retrospective study enrolled 104 patients who underwent lobectomy by video-assisted thoracic surgery. Pulmonary function tests were performed preoperatively and postoperatively at 3, 6 and 12 months. We investigated time-dependent changes in FEV1. In addition, the ratio of measured to predicted postoperative FEV1 calculated by the subsegmental method was evaluated to identify the factors associated with variations in postoperative FEV1.

RESULTS

Compared with the predicted postoperative FEV1, the measured postoperative FEV1 was 8% higher at 3 months, 11% higher at 6 months and 13% higher at 12 months. The measured postoperative FEV1 significantly increased from 3 to 6 months (P = 0.002) and from 6 to 12 months (P = 0.015) after lobectomy resected lobe, smoking history and body mass index were significant factors associated with the ratio of measured to predicted postoperative FEV1 at 12 months (P < 0.001, P = 0.036 and P = 0.025, respectively).

CONCLUSIONS

Postoperative FEV1 increased up to 12 months after lobectomy by video-assisted thoracic surgery. The predicted postoperative pulmonary function was underestimated after 3 months, particularly after lower lobectomy.
Comparing outcomes in patients with end-stage chronic obstructive pulmonary disease: single versus bilateral lung transplants
Authors: Mutyala Sudeep , Kashem M Abul , Kanaparthi Jay , Sunagawa Gengo , Suryapalam Manish , Leotta Eros , Minakata Kenji , Brann Stacey , Shigemura Norihisa , Toyoda Yoshiya
Published: May 2021

OBJECTIVES

Debate continues on whether a bilateral (BLT) or a single lung transplantation (SLT) is preferred for patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study is to examine the interplay between patient age and transplant type on survival outcomes.

METHODS

We performed a retrospective study of lung transplants for COPD at our centre from February 2012 to March 2020 (n = 186). Demographics and clinical parameters were compared between patients based on their age (≤65 vs >65 years old) and type of transplant (single vs bilateral). Cox proportional hazards regression was also performed. P-values <0.05 were considered significant.

RESULTS

Of the 186 patients with COPD who received lung transplants, 71 (38.2%) received BLTs and 115 (61.8%) received SLTs. There was no significant difference in survival outcomes when looking at patients with single versus BLTs (P = 0.870). There was also no difference in survival between the 2 age groups ≤65 versus > 65 years (P = 0.723). The Cox model itself also did not show a statistically significant improvement in survival outcomes (P = 0.126).

CONCLUSIONS

Lung transplant outcomes in patients with end-stage COPD demonstrated non-inferior results in patients with an SLT compared to patients with a BLT. When we compared the age groups, neither transplant type showed superior survival benefits, suggesting there may be some utility in an SLT in younger recipients.
Anti–PD-L1 Therapy Does Not Improve Survival in a Murine Model of Lethal Staphylococcus aureus Pneumonia
Authors: Curran Colleen S , Busch Lindsay M , Li Yan , Xizhong Cui , Sun Junfeng , Eichacker Peter Q , Torabi-Parizi Parizad
Published: May 2021

Background

Staphylococcus aureus (SA) bacterial pneumonia is a common cause of sepsis in intensive care units. Immune checkpoint inhibitors (CPIs) that target programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have been proposed for the treatment of sepsis. However, in our systematic review of sepsis preclinical models, none of the models examined CPIs in pneumonia.

Methods

Mice were inoculated intratracheally with vehicle control, low dose (LD)- or high dose (HD)-SA. Immune cell recruitment and checkpoint molecule expression were examined at 4, 24, and 48 hours after infection. Infected animals, treated with control or anti–PD-L1 antibodies, were assessed for survival, bacterial burden, lung immunophenotypes, and mediator production.

Results

LD-SA and HD-SA produced lethality of 15% and 70%, respectively, by 168 hours. At 24 hours, LD-infected animals exhibited increased lung monocyte PD-L1 expression (P = .0002) but lower bacterial counts (P = .0002) compared with HD animals. By 48 hours, either infection induced lung neutrophil and macrophage PD-L1 expression (P < .0001). Anti–PD-L1 treatment at the time of infection and at 24 hours following infection with low to high doses of SA reduced PD-L1 detection but did not affect survival or bacterial clearance.

Conclusions

Anti–PD-L1 therapy did not alter survival in this pneumonia model. Preclinical studies of additional common pathogens and septic foci are needed.
Peripheral Plasmodium falciparum Infection in Early Pregnancy Is Associated With Increased Maternal Microchimerism in the Offspring
Authors: Simon Neta , Shallat Jaclyn , Houck John , Jagannathan Prasanna , Prahl Mary , Muhindo Mary K , Kakuru Abel , Olwoch Peter , Feeney Margaret E , Harrington Whitney E
Published: May 2021

Background

Placental malaria has been associated with increased cord blood maternal microchimerism (MMc), which in turn may affect susceptibility to malaria in the offspring. We sought to determine the impact of maternal peripheral Plasmodium falciparum parasitemia during pregnancy on MMc and to determine whether maternal cells expand during primary parasitemia in the offspring.

Methods

We conducted a nested cohort study of maternal-infant pairs from a prior pregnancy malaria chemoprevention study. Maternal microchimerism was measured by quantitative polymerase chain reaction targeting a maternal-specific marker in genomic DNA from cord blood, first P falciparum parasitemia, and preparasitemia. Logistic and negative binomial regression were used to assess the impact of maternal peripheral parasitemia, symptomatic malaria, and placental malaria on cord blood MMc. Generalized estimating equations were used to assess predictors of MMc during infancy.

Results

Early maternal parasitemia was associated with increased detection of cord blood MMc (adjusted odds ratio = 3.91, P = .03), whereas late parasitemia, symptomatic malaria, and placental malaria were not. The first parasitemia episode in the infant was not associated with increased MMc relative to preparasitemia.

Conclusions

Maternal parasitemia early in pregnancy may increase the amount of MMc acquired by the fetus. Future work should investigate the impact of this MMc on immune responses in the offspring.
The Logic of Ceasefires in Civil War
Authors: Clayton Govinda , Sticher Valerie
Published: May 2021

Ceasefires play a role in almost all civil war peace processes. Yet existing studies undertheorize the ways in which different logics drive the design of ceasefire agreements, and the effect this has on violence suspension. Building on bargaining theory and existing ceasefire literature, we identify different bargaining problems conflict parties face over the course of a conflict, and three classes of ceasefire design they use to address these problems. We argue that the effect of ceasefires is driven both by these underlying logics and by the provisions they contain. Building on the PA-X data to capture the provisions included within all written civil war ceasefires between 1990 and 2019, and using Uppsala Conflict Data Program georeferenced event data, we estimate models of ceasefire survival, with conflict deaths as the main measure of whether a ceasefire remains in place. We find that definitive ceasefires (i.e., agreements with demobilization and incompatibility provisions), followed by preliminary ceasefires (i.e., agreements with compliance mechanisms), are associated with longer periods of violence suspension than cessation of hostilities agreements that lack such provisions. We discuss the implications of our results for conflict parties and third parties seeking to facilitate the transition from war to peace.
Seeing in Mirrors
Authors: Voltolini Alberto
Published: May 2021

Notwithstanding Plato’s venerable opinion, many people nowadays claim either that mirrors are not pictures, or that, if they are such, they are just transparent pictures in Kendall Walton’s sense of a particular kind of picture (causally based representations, Peircean indexes, namely, natural signs, which are grasped by means of a perceptual experience of transparency—seeing-through—that lets one literally see the object perceived through the picture). In this article, however, I want to argue that mirrors are bona fide pictures. For they are grasped via what, as I assume in the article, makes a picture a picture, that is, a representation with a figurative value, namely, a depiction; namely, a certain seeing-in experience. This is the sui generis perceptual experience that Richard Wollheim originally appealed to. Once this experience is suitably reconceived, one can show how it successfully applies to mirrors as well, in order to prove that they are bona fide pictures. From an aesthetical point of view, this is an important result. For it shows that the class of pictures is broader than what people nowadays think and is closer to the original intuition sustaining Plato’s opinion.
Monitoring outpatient antibiotic utilization using reimbursement and retail sales data: a population-based comparison in France, 2012–17
Authors: Trinh Nhung T. H. , Chalumeau Martin , Bruckner Tim A. , Levy Corinne , Bessou Antoine , Milic Dejan , Cohen Robert , Lemaitre Magali , Cohen Jérémie F.
Published: May 2021

Objectives

To assess whether a retail sales database could be used to monitor antibiotic utilization in the outpatient setting at the national level.

Methods

We extracted 2012–17 outpatient antibiotic extrapolated retail sales (IQVIA’s Xponent) and reimbursement data from the National Health Insurance (SNDS) in metropolitan France. We compared estimates of antibiotic use and consumption [number of antibiotic drug deliveries (DrID) and defined daily doses (DID) per 1000 inhabitants per day]. We relied on relative differences, Pearson’s r statistics and time series using autoregressive integrated moving average (ARIMA) modelling to study: (i) differences in point estimates, (ii) correlation, and (iii) consistency in time trends between Xponent and SNDS. The analysis was conducted overall and in subgroups (age groups, therapeutic classes, major antimicrobial agents and regions).

Results

We analysed approximately 377 million antibiotic drug deliveries, comprising nearly 3.4 billion DDDs. Overall, Xponent slightly overestimated SNDS point estimates with yearly relative differences of +3.5% for DrID and +3.3% for DID. Peaks in relative differences were observed for July and August months. Relative differences were <5% in most subgroups, except for fosfomycin and three French regions. Overall and across most subgroups, the correlation between Xponent and SNDS monthly aggregated estimates was almost perfect (r ≥ 0.992 for all subgroups, except for one region). ARIMA modelling showed high consistency between Xponent’s and SDNS’s DrID time series, but detected timepoints where the series significantly diverged.

Conclusions

IQVIA’s Xponent and SNDS data were highly consistent. Xponent database seems suitable for monitoring outpatient antibiotic utilization in France.
Molecular and genomic epidemiology of VIM/IMP-like metallo-β-lactamase-producing Pseudomonas aeruginosa genotypes in Poland
Authors: Urbanowicz P. , Izdebski R. , Baraniak A. , Żabicka D. , Hryniewicz W. , Gniadkowski M.
Published: May 2021

Objectives

To identify key factors of the expansion of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa (MPPA) in Poland, focusing on the role of clonal epidemic(s).

Methods

MPPA isolates were typed by PFGE, followed by MLST. blaVIM/IMP MBL genes were amplified and sequenced within class 1 integrons. Their location was assessed by S1 nuclease-hybridization assays. Short-read WGS was performed, and genomes were subjected to SNP-based phylogenetic and resistome analyses.

Results

Of 1314 MPPA isolates collected in 2005–15 from 212 hospitals, 454 representatives were selected. The isolates belonged to 120 pulsotypes and 52 STs, of which ST235 (∼31%), ST111 (∼17%), ST273 (∼16%) and ST654 (∼9%) prevailed, followed by ST244, ST17, ST395, ST175 and ST1567. The isolates produced seven VIM variants (97.5%) and four IMPs encoded by 46 integrons, most of which were observed only or mainly in Poland. Around 60% of the isolates resulted from (inter)regional clonal outbreaks of 10 individual ST235, ST111, ST273 and ST654 genotypes. The phylogenetic analysis of 163 genomes revealed heterogeneity of ST235 and ST111 populations, arising from transnational circulation and on-site differentiation of several clades/branches. Contrarily, ST273 and ST654 formed relatively homogeneous and apparently Poland-specific lineages, and a unique ST273 genotype with integron In249 was the most expansive organism.

Conclusions

Together with a previous report on self-transmissible In461-carrying IncP-2-type plasmids, this study revealed the molecular/genomic background of the rapid MPPA increase in Poland in 2001–15, evidencing multi-clonal spread as its leading factor. Numerous novel/specific MPPA characteristics were identified.
Mining Consumer Minds: Downstream Consequences of Host Motivations for Home-Sharing Platforms
Authors: Chung Jaeyeon (Jae) , Johar Gita Venkataramani , Li Yanyan , Netzer Oded , Pearson Matthew
Published: May 2021

This research sheds light on consumer motivations for participating in the sharing economy and examines downstream consequences of the uncovered motivations. We use text-mining techniques to extract Airbnb hosts’ motivations from their responses to the question “why did you start hosting.” We find that hosts are driven not only by the monetary motivation “to earn cash” but also by intrinsic motivations such as “to share beauty” and “to meet people.” Using extensive transaction-level data, we find that hosts with intrinsic motivations post more property photos and write longer property descriptions, demonstrating greater engagement with the platform. Consequently, these hosts receive higher guest satisfaction ratings. Compared to hosts who want to earn cash, hosts motivated to meet people are more likely to keep hosting and to stay active on the platform, and hosts motivated to share beauty charge higher prices. As a result, these intrinsically motivated hosts have a higher customer lifetime value compared to those with a monetary motivation. We employ a multimethod approach including text mining, Bayesian latent attrition models, and lab experiments to derive these insights. Our research provides an easy-to-implement approach to uncovering consumer motivations in practice and highlights the consequential role of these motivations for firms.
Impact of Triflumuron onHalyomorpha halys(Hemiptera: Pentatomidae): Laboratory and Field Studies
Authors: Masetti Antonio , Depalo Laura , Pasqualini Edison
Published: May 2021

Halyomorpha halys, (the brown marmorated stink bug, BMSB), is a high-concern invasive species causing severe damage to orchards in many countries outside its native Asian range. Control options matching both effectiveness and sustainability are currently lacking. Inhibitors of chitin biosynthesis might be exploited for integrated management programs because of the overall better ecotoxicological profile in comparison with most neurotoxic insecticides used so far against BMSB. In this study, the activity of triflumuron, a benzoylphenyl urea hampering chitin biosynthesis, was tested on BMSB in laboratory and field conditions. In laboratory bioassays, the insecticide was sprayed on potted peach plants (30 cm high) and residues were aged in a glasshouse for 0, 7, 14, and 21 d. Then, third-instar bugs were placed on the plants and continuously exposed to residues. Mortality was scored after 7, 14, and 21 d exposure. Triflumuron caused significantly higher mortality on BMSB nymphs in comparison with water controls at all aging periods. Moreover, aging of residues up to 21 d did not cause any significant reduction of activity. Field experiments were also carried out in 2019 in eight pear orchards. Injuries to fruits at harvest were compared between plots where triflumuron was added to insecticide sprays against BMSB and control plots managed exactly in the same way but without any triflumuron treatment. An overall mean of 9.99 ± 1.98% stink bug injured fruits was detected in plots managed with the strategy including triflumuron, whereas 19.45 ± 3.55% of fruits were injured in plots assigned to controls.
From Extra-Territorial Leverage and Transnational Environmental Protection to Distortions of Competition: The Level Playing Field in the EU–UK Trade and Cooperation Agreement
Authors: Leonelli Giulia Claudia
Published: May 2021

This article inquires to what extent the European Union (EU)–UK Trade and Cooperation Agreement (TCA) may help safeguard high levels of transnational environmental protection, taking into consideration potential reductions in UK levels of protection and the ensuing effects. The article encompasses an analysis of the Trade and Sustainable Development (TSD) Chapters in recent EU trade or trade and investment Agreements (FTAs); in this respect, it emphasises that the TCA’s provisions are innovative. However, the TCA has marked a shift from the EU’s initial attempts to exercise its extra-territorial leverage and push for high levels of transnational environmental protection to a focus on the stricto sensu economic level playing field. This narrow focus cannot possibly capture many aspects of environmental protection. The article thus concludes that, from an environmental perspective, the TCA’s provisions are far from ambitious. Further, it develops some considerations on the way forward for the EU institutions, as they start to rethink their approach to TSD Chapters.
Reading the Mahābhārata as Śāstra: The Role of the ‘Righteous’ Pāṇḍavas and ‘Villainous’ Kauravas in Madhva's Dvaitavedānta
Authors: Sharma Vishal
Published: May 2021

The Sanskrit Mahābhārata is considered to be a śāstra in Mādhva Vaiṣṇavism, and Madhva composed one of the earliest treatises dedicated to explaining the Mahābhārata’s deeper meaning. In doing so, he pays careful attention to the distinction between the righteous Pāṇḍavas and corrupt Kauravas—a distinction that exists in theory if not always in practice. How does Madhva demarcate the Kauravas and the Pāṇḍavas, and why does this matter for his own theology? Looking at two episodes that either blur or upend the demarcation of the Kauravas and Pāṇḍavas, the mace-battle between Bhīma and Duryodhana (9.60) and the Pāṇḍavas’ journey to heaven (17-18.3), this article shows how Madhva’s Mahābhāratatātparyanirṇaya explains key tenets of Madhva’s ontology and theology. When read carefully, each episode brings out important features of Madhva’s doctrine of devatātāratamya—the gradation of gods. Rather than simply understanding Madhva’s commentary as a theologisation or vedānticisation of the narrative, I argue that his exegesis itself develops and explains central doctrines of Dvaitavedānta, particularly tāratamya and aparokṣajñāna. Vedānticization, in this understanding then, is not simply bringing forth an interpretation of the narrative that fits one's prior philosophical commitments, but it is a process of constituting theology through the narrative.
Universal forensic DNA databases: acceptable or illegal under the European Court of Human Rights regime?
Authors: Tuazon Oliver M
Published: May 2021

Universal forensic DNA databases are controversial privacy-wise given their omnibus scope of incorporating DNA profile data of the entire population into the system. Following the landmark decision of the European Court of Human Rights on the retention of DNA profiles in S. and Marper v. the United Kingdom, two differing opinions emerged on its application to universal databases: their acceptability and illegality. This paper makes use of the elements of the right to respect for private life (Article 8 ECHR), distilled from the Court’s jurisprudence involving collection and retention of DNA profile data, in the form of tests—preliminary interference, legality, legitimate purpose, and proportionality—in assessing the feasibility of establishing population-wide DNA databases in Europe.
A rare case of pancreatic head hydatid cyst
Authors: Qarmo Muhammad M , Aldirani Alaa N , Al-Boukhari Lynn M J , Moussa Faisal M , Alkhateeb Lama A
Published: May 2021

Hydatidosis or Echinococcosis is a parasitic disease caused by infection with the larval stage of Echinococcus granulosus. Primary isolated pancreatic hydatidosis is very rare even in countries where echinococcosis disease is highly endemic. The objective of this case report is to highlight this unusual and rare hydatid cyst presentation to avoid incorrect diagnosis and management. In our case, preoperative evaluation guided the diagnosis toward cystic pancreatic neoplasms, leading us to contemplate a radical surgical approach (Pancreaticoduodenectomy). Pancreatic hydatid cysts can be confused with cystic pancreatic neoplasms, it should always be considered as a differential diagnosis in endemic areas, to prevent misdiagnosis and inappropriate management.
Fresnel models for gravitational wave effects on pulsar timing
Authors: McGrath Casey , Creighton Jolien
Published: May 2021

Merging supermassive black hole binaries produce low-frequency gravitational waves, which pulsar timing experiments are searching for. Much of the current theory is developed within the plane-wave formalism, and here we develop the more general Fresnel formalism. We show that Fresnel corrections to gravitational wave timing residual models allow novel measurements to be made, such as direct measurements of the source distance from the timing residual phase and frequency, as well as direct measurements of chirp mass from a monochromatic source. Probing the Fresnel corrections in these models will require future pulsar timing arrays with more distant pulsars across our Galaxy (ideally at the distance of the Magellanic Clouds), timed with precisions less than 100 ns, with distance uncertainties reduced to the order of the gravitational wavelength. We find that sources with chirp mass of order 109 M⊙ and orbital frequency ω0 > 10 nHz are good candidates for probing Fresnel corrections. With these conditions met, the measured source distance uncertainty can be made less than 10 per cent of the distance to the source for sources out to ∼100 Mpc, source sky localization can be reduced to sub-arcminute precision, and source volume localization can be made to less than 1 Mpc3 for sources out to 1-Gpc distances.
The hybrid radio/X-ray correlation of the black hole transient MAXI J1348–630
Authors: Carotenuto F , Corbel S , Tremou E , Russell T D , Tzioumis A , Fender R P , Woudt P A , Motta S E , Miller-Jones J C A , Tetarenko A J , Sivakoff G R
Published: May 2021

Black hole (BH) low mass X-ray binaries in their hard spectral state are found to display two different correlations between the radio emission from the compact jets and the X-ray emission from the inner accretion flow. Here, we present a large data set of quasi-simultaneous radio and X-ray observations of the recently discovered accreting BH MAXI J1348–630 during its 2019/2020 outburst. Our results span almost six orders of magnitude in X-ray luminosity, allowing us to probe the accretion–ejection coupling from the brightest to the faintest phases of the outburst. We find that MAXI J1348–630 belongs to the growing population of outliers at the highest observed luminosities. Interestingly, MAXI J1348–630 deviates from the outlier track at LX ≲ 7 × 1035(D/2.2  kpc)2 erg s−1 and ultimately rejoins the standard track at LX ≃ 1033(D/2.2 kpc)2 erg s−1, displaying a hybrid radio/X-ray correlation, observed only in a handful of sources. However, for MAXI J1348–630 these transitions happen at luminosities much lower than what observed for similar sources (at least an order of magnitude). We discuss the behaviour of MAXI J1348–630 in light of the currently proposed scenarios and highlight the importance of future deep monitorings of hybrid correlation sources, especially close to the transitions and in the low luminosity regime.
The conserved sex regulator DMRT1 recruits SOX9 in sexual cell fate reprogramming
Authors: Lindeman Robin E , Murphy Mark W , Agrimson Kellie S , Gewiss Rachel L , Bardwell Vivian J , Gearhart Micah D , Zarkower David
Published: May 2021

Mammalian sexual development commences when fetal bipotential progenitor cells adopt male Sertoli (in XY) or female granulosa (in XX) gonadal cell fates. Differentiation of these cells involves extensive divergence in chromatin state and gene expression, reflecting distinct roles in sexual differentiation and gametogenesis. Surprisingly, differentiated gonadal cell fates require active maintenance through postnatal life to prevent sexual transdifferentiation and female cell fate can be reprogrammed by ectopic expression of the sex regulator DMRT1. Here we examine how DMRT1 reprograms granulosa cells to Sertoli-like cells in vivo and in culture. We define postnatal sex-biased gene expression programs and identify three-dimensional chromatin contacts and differentially accessible chromatin regions (DARs) associated with differentially expressed genes. Using a conditional transgene we find DMRT1 only partially reprograms the ovarian transcriptome in the absence of SOX9 and its paralog SOX8, indicating that these factors functionally cooperate with DMRT1. ATAC-seq and ChIP-seq show that DMRT1 induces formation of many DARs that it binds with SOX9, and DMRT1 is required for binding of SOX9 at most of these. We suggest that DMRT1 can act as a pioneer factor to open chromatin and allow binding of SOX9, which then cooperates with DMRT1 to reprogram sexual cell fate.
DGLinker: flexible knowledge-graph prediction of disease–gene associations
Authors: Hu Jiajing , Lepore Rosalba , Dobson Richard J B , Al-Chalabi Ammar , M. Bean Daniel , Iacoangeli Alfredo
Published: May 2021

As a result of the advent of high-throughput technologies, there has been rapid progress in our understanding of the genetics underlying biological processes. However, despite such advances, the genetic landscape of human diseases has only marginally been disclosed. Exploiting the present availability of large amounts of biological and phenotypic data, we can use our current understanding of disease genetics to train machine learning models to predict novel genetic factors associated with the disease. To this end, we developed DGLinker, a webserver for the prediction of novel candidate genes for human diseases given a set of known disease genes. DGLinker has a user-friendly interface that allows non-expert users to exploit biomedical information from a wide range of biological and phenotypic databases, and/or to upload their own data, to generate a knowledge-graph and use machine learning to predict new disease-associated genes. The webserver includes tools to explore and interpret the results and generates publication-ready figures. DGLinker is available at https://dglinker.rosalind.kcl.ac.uk. The webserver is free and open to all users without the need for registration.
The H3K36me2 methyltransferase NSD1 modulates H3K27ac at active enhancers to safeguard gene expression
Authors: Fang Yuan , Tang Yin , Zhang Yanjun , Pan Yixin , Jia Junqi , Sun Zhongxing , Zeng Weiwu , Chen Jiaqi , Yuan Ying , Fang Dong
Published: May 2021

Epigenetics, especially histone marks, functions beyond the DNA sequences to regulate gene expression. Depletion of NSD1, which catalyzes H3K36me2, leads to both up- and down-regulation of gene expression, indicating NSD1 is associated with both active and repressed gene expression. It's known that NSD1 regulates the deposition and expansion of H3K27me3, a repressive mark for gene expression, to keep active gene transcription. However, how NSD1 functions to repress gene expression is largely unknown. Here, we find that, when NSD1 is knocked out in mouse embryonic stem cells (mESCs), H3K27ac increases correlatively with the decrease of H3K36me2 at active enhancers, which is associated with mesoderm differentiation genes, leading to elevated gene expression. Mechanistically, NSD1 recruits HDAC1, the deacetylase of H3K27ac, to chromatin. Moreover, HDAC1 knockout (KO) recapitulates the increase of H3K27ac at active enhancers as the NSD1 depletion. Together, we propose that NSD1 deposits H3K36me2 and recruits HDAC1 at active enhancers to serve as a ‘safeguard’, preventing further activation of active enhancer-associated genes.
Tackling Smoker Misperceptions About E-cigarettes Using Expert Videos
Authors: Svenson Madeleine , Green James , Maynard Olivia M
Published: May 2021

Background

The pervasive misperception that e-cigarettes are equally or more harmful than combustible cigarettes is a barrier to current smokers switching to e-cigarettes. To tackle misperceptions, public health bodies are using informational videos, although their efficacy is unknown.

Methods

In our online study, current UK smokers who do not vape (n = 382) were randomized to view either: (1) a Cancer Research UK (CRUK) text-only video; (2) a video featuring leading e-cigarette experts (expert); or (3) a no video control condition, and then completed questions regarding e-cigarette harm perceptions.

Results

Compared to the control condition, participants in the CRUK condition, and especially those in the expert condition had more accurate harm perceptions of e-cigarettes and had more accurate knowledge of e-cigarette constituents. In the expert condition, 67% of individuals reported they would try an e-cigarette in a future quit attempt, compared with 51% in the CRUK condition and 35% in the control condition.

Conclusions

Our findings are encouraging in the face of mounting evidence that e-cigarette misperceptions are increasing. Whilst misperceptions are often characterized as resistant to correction, we find that carefully designed public health information videos have the potential to promote a more accurate, informed view of e-cigarettes, and encourage intended e-cigarette use among UK smokers. Importantly, we find this among current smokers who do not vape, a group often reported as having the highest levels of misperceptions and as having the most to gain from accurate e-cigarette perceptions.

Implications

There is mounting evidence that e-cigarette misperceptions are increasing, particularly among smokers who do not vape, a group who have most to gain from accurate information about e-cigarettes. Misperceptions are often characterized as difficult to change and there is relatively little research on how to correct e-cigarette misperceptions. Our research in the UK shows that, compared to controls, e-cigarette misperceptions can be corrected among those smokers who are shown carefully constructed expert videos. This work has important implications for the development and dissemination of these important messages.
Identification and utilization of genetic determinants of trait measurement errors in image-based, high-throughput phenotyping
Authors: Zhou Yan , Kusmec Aaron , Mirnezami Seyed Vahid , Attigala Lakshmi , Srinivasan Srikant , Jubery Talukder Z. , Schnable James C. , Salas-Fernandez Maria G. , Ganapathysubramanian Baskar , Schnable Patrick S.
Published: May 2021

The accuracy of trait measurements greatly affects the quality of genetic analyses. During automated phenotyping, trait measurement errors, i.e. differences between automatically extracted trait values and ground truth, are often treated as random effects that can be controlled by increasing population sizes and/or replication number. In contrast, there is some evidence that trait measurement errors may be partially under genetic control. Consistent with this hypothesis, we observed substantial nonrandom, genetic contributions to trait measurement errors for five maize (Zea mays) tassel traits collected using an image-based phenotyping platform. The phenotyping accuracy varied according to whether a tassel exhibited “open” versus. “closed” branching architecture, which is itself under genetic control. Trait-associated SNPs (TASs) identified via genome-wide association studies (GWASs) conducted on five tassel traits that had been phenotyped both manually (i.e. ground truth) and via feature extraction from images exhibit little overlap. Furthermore, identification of TASs from GWASs conducted on the differences between the two values indicated that a fraction of measurement error is under genetic control. Similar results were obtained in a sorghum (Sorghum bicolor) plant height dataset, demonstrating that trait measurement error is genetically determined in multiple species and traits. Trait measurement bias cannot be controlled by increasing population size and/or replication number.
Cellular export of sugars and amino acids: role in feeding other cells and organisms
Authors: Kim Ji-Yun , Loo Eliza P -I , Pang Tin Yau , Lercher Martin , Frommer Wolf B , Wudick Michael M
Published: May 2021

Sucrose, hexoses, and raffinose play key roles in the plant metabolism. Sucrose and raffinose, produced by photosynthesis, are translocated from leaves to flowers, developing seeds and roots. Translocation occurs in the sieve elements or sieve tubes of angiosperms. But how is sucrose loaded into and unloaded from the sieve elements? There seem to be two principal routes: one through plasmodesmata and one via the apoplasm. The best-studied transporters are the H+/SUCROSE TRANSPORTERs (SUTs) in the sieve element-companion cell complex. Sucrose is delivered to SUTs by SWEET sugar uniporters that release these key metabolites into the apoplasmic space. The H+/amino acid permeases and the UmamiT amino acid transporters are hypothesized to play analogous roles as the SUT-SWEET pair to transport amino acids. SWEETs and UmamiTs also act in many other important processes—for example, seed filling, nectar secretion, and pollen nutrition. We present information on cell type-specific enrichment of SWEET and UmamiT family members and propose several members to play redundant roles in the efflux of sucrose and amino acids across different cell types in the leaf. Pathogens hijack SWEETs and thus represent a major susceptibility of the plant. Here, we provide an update on the status of research on intercellular and long-distance translocation of key metabolites such as sucrose and amino acids, communication of the plants with the root microbiota via root exudates, discuss the existence of transporters for other important metabolites and provide potential perspectives that may direct future research activities.
A microProtein repressor complex in the shoot meristem controls the transition to flowering
Authors: Rodrigues Vandasue L. , Dolde Ulla , Sun Bin , Blaakmeer Anko , Straub Daniel , Eguen Tenai , Botterweg-Paredes Esther , Hong Shinyoung , Graeff Moritz , Li Man-Wah , Gendron Joshua M. , Wenkel Stephan
Published: May 2021

MicroProteins are potent post-translational regulators. In Arabidopsis (Arabidopsis thaliana), the miP1a/b microProteins delay floral transition by forming a complex with CONSTANS (CO) and the co-repressor protein TOPLESS. To better understand the function of the miP1a microProtein in floral repression, we performed a genetic suppressor screen to identify suppressors of miP1a (sum) function. One mutant, sum1, exhibited strong suppression of the miP1a-induced late-flowering phenotype. Mapping of sum1 identified another allele of the gene encoding the histone H3K4 demethylase JUMONJI14 (JMJ14), which is required for miP1a function. Plants carrying mutations in JMJ14 exhibit an early flowering phenotype that is largely dependent on CO activity, supporting an additional role for CO in the repressive complex. We further investigated whether miP1a function involves chromatin modification, performed whole-genome methylome sequencing studies with plants ectopically expressing miP1a, and identified differentially methylated regions (DMRs). Among these DMRs is the promoter of FLOWERING LOCUS T (FT), the prime target of miP1a that is ectopically methylated in a JMJ14-dependent manner. Moreover, when aberrantly expressed at the shoot apex, CO induces early flowering, but only when JMJ14 is mutated. Detailed analysis of the genetic interaction among CO, JMJ14, miP1a/b, and TPL revealed a potential role for CO as a repressor of flowering in the shoot apical meristem (SAM). Altogether, our results suggest that a repressor complex operates in the SAM, likely to maintain it in an undifferentiated state until leaf-derived florigen signals induce SAM conversion into a floral meristem.
Microstructure and continuous phase transition of a regular Hayward black hole in anti-de Sitter spacetime
Authors: Naveena Kumara A , Ahmed Rizwan C L , Hegde Kartheek , Ali Md Sabir , Ajith K M
Published: May 2021

In this article we study the thermodynamic phase transition of a regular Hayward-AdS black hole, by introducing a new order parameter, which is the potential conjugate to the magnetic charge arising from a non-linearly coupled electromagnetic field. We use Landau continuous phase transition theory to discuss the van der Waals-like critical phenomena of the black hole. The well-known interpretation of the phase transition of an AdS black hole as being a large and small black hole transition is re-interpreted as being a transition between a high-potential phase and a low-potential phase. The microstructure associated with this phase transition is studied using the Ruppeiner geometry. By investigating the behaviour of the Ruppeiner scalar curvature, we find that charged and uncharged (effective) molecules of the black hole have distinct microstructure, which is analogous to that of fermion and boson gas.
Creating an e-cohort of individuals with lived experience of homelessness and subsequent mortality in Wales, UK
Authors: Song Jiao , Grey Charlotte N B , Davies Alisha R
Published: May 2021

Background

Homelessness is an extreme form of social exclusion, with homeless people experiencing considerable social and health inequities. Estimates of morbidity and mortality amongst homeless populations is limited due to the lack of recording of housing status across health datasets. The aim of this study is to: (i) identify a homelessness e-cohort by linking routine health data in Wales, and (ii) explore whether a period of reported past homelessness, places this population at greater risk of morbidity and mortality.

Methods

Homelessness identified through linkage across primary, secondary care and substance misuse datasets in the Secure Anonymised Information Linkage (SAIL) Databank. Mortality was examined through linkage to the Office for National Statistics mortality data.

Results

E-cohort of 15 472 individuals with lived experience of homelessness identified. Of those, 21 individuals died between February and July 2020 involving coronavirus disease of 2019 (COVID-19). Those with lived experience of homelessness had increased mortality from many causes including accidents, liver diseases and suicides.

Conclusion

Linking multiple routine datasets provides a more comprehensive dataset of a marginalized population, including individuals who are not included in government homeless statistics. Application of the cohort demonstrated that individuals with lived experience of homelessness have increased mortality involving COVID-19 and other causes. The underlying reasons, health needs and causes of death warrant further exploration.
The extrapyramidal syndromes of chronic kidney disease and dialysis (EPS-CKDD): diagnostic criteria, risk factors and prognosis
Authors: Manickavasagar R , Chemmanam T , Youssef A , Agarwal A , Prentice D A , Irish A B
Published: May 2021

Background

Acute extrapyramidal movement disorders in dialysis patients are rare, inconsistently defined and have uncertain aetiology and prognosis.

Aim

Define diagnostic criteria, prognosis and risk factors

Design and Methods

Retrospective case series review of 20 patients (14 female, mean age 62 years) receiving dialysis for a median of 15 (interquartile range 4–35) months who presented with acute parkinsonism (AP = 11) or chorea/athetosis (CA = 9).

Results

All patients had type 2 diabetes (HbA1c 6.8 ± 1.0) and had received metformin. Lactic acidosis was present in 2 patients at presentation and serum lactate was elevated in 7/15 patients tested. No patient had abnormal copper or thyroid metabolism and 5/8 patients tested returned marginal abnormalities in heavy metal screening. Magnetic resonance imaging (MRI) revealed characteristic bilateral symmetric T2 hyperintensity of the basal ganglia (BG), predominantly putamen and globus pallidus (the lentiform nucleus) and more extensive involvement of the external and internal capsules in patients with AP presentation. Post-mortem demonstrated cytotoxic necrosis of the BG. Therapy included thiamine, intensive dialysis and cessation of metformin. Two patients died acutely, nine recovered and nine had residual symptoms. Median survival did not differ by presentation: AP 24 [95% confidence interval (CI) 21–27] and CA 33 (95% CI 32–35) months, P = 0.21.

Conclusions

There are two distinct clinical extrapyramidal movement disorders associated with specific diagnostic MRI imaging that support the diagnosis of the extrapyramidal syndromes of chronic kidney disease and dialysis. The associations with diabetes, metformin and metabolic acidosis suggest a common pathogenic mechanism but require additional study. Early recognition and treatment may improve outcomes.