bluuebunny/crossref_metadata_2025 huggingface dataset:
Bronchiectasis
Authors: Robinson Terry , Scullion Jane
Published: March 2021

Bronchiectasis is defined as irreversible bronchial wall dilatation and thickening. It may present clinically with recurrent chest infections, cough, chronic sputum production, shortness of breath, pleuritic chest pain, fatigue, and malaise. It can occur as a result of a primary infection, toxic insult occurring at any time from childhood to late adulthood, immunodeficiencies, some inflammatory conditions, and some inherited conditions such as primary ciliary dyskinesia and cystic fibrosis, but in approximately 50% of cases no underlying cause is found. This chapter covers the causes, clinical features, and management of bronchiectasis, including antibiotic treatment. Other infections that may occur are also explained, and monitoring regimes are indicated.
Interstitial lung disease (ILD)
Authors: Robinson Terry , Scullion Jane
Published: March 2021

The interstitial lung diseases (ILDs), are an extensive range of lung diseases, rather than a single disease entity. These diseases are often grouped together because they have similarities in clinical presentation, radiographic changes, physiological features, and symptoms. Despite their similarities, these diseases have a variety of aetiologies, treatments, and prognoses. The rate of onset of symptoms is very variable. Some patients present with long-standing radiological symptoms, often found opportunistically. Other patients present with acute onset symptoms, rapidly developing respiratory failure and ultimately progressing to death. This chapter covers the presentation, clinical findings, diagnosis, common causes, and associated investigations. Common ILDs are also described.
Oxygen therapy
Authors: Robinson Terry , Scullion Jane
Published: March 2021

Oxygen therapy is the administration of supplementary oxygen to achieve a higher inspiration of oxygen than is achieved when breathing air. Oxygen therapy aims to correct hypoxaemia. This chapter covers the clinical indicators of hypoxaemia, the use of acute oxygen therapy, the choice of high-flow or low-flow devices, and examples of different types of each. Humidification of acute oxygen therapy is also covered, and the points to consider such as the risk of encouraging bacterial growth. The evidence base for long-term oxygen therapy (LTOT) is outlined, as well as assessment by the respiratory team for prescribing the treatment. Intermittent oxygen therapy, ambulatory oxygen, and oxygen containers are all covered. Home oxygen and follow-up care are both covered.
Violent radicalization and terrorism: A societal challenge for all citizens
Authors: Bhui Kamaldeep , Bhugra Dinesh
Published: March 2021

We set out the remarkable range of contributors to this important and searching set of chapters, which demonstrate interdisciplinary perspectives on how to understand and then prevent terrorism. The authors are scholars and practitioners, and are embedded in their work on a daily basis in systems that tenaciously seek to tackle terrorism on a global scale, as well as in their localities. The perspectives include cultural, religious, legal, political, public health, and youth and adult life course approaches, as well as how national and local governments perceive the challenge and respond, sometimes helpfully and sometimes not.
Police–community relations and cultural competency: Important means of countering violent extremism
Authors: Lashley Myrna , Hassan Ghayda , Thompson Sara , Chartrand Michael , Touzin Serge
Published: March 2021

Cultural competency may be helpful to police in fighting violent extremism. Perceived cultural competency of security officers may directly affect citizens responses, especially individuals from vulnerable communities. Police often need to depend upon citizens’ cooperation to identify those who may be engaging in activities of violent extremism. Therefore, officers must be trained in cultural competency to help reduce feelings of citizen alienation. Participants from three Canadian cities completed an online survey concerning perceptions of police cultural competence in several areas, including national security. Results were discussed with focus groups. With cultural variations, citizens were mostly satisfied with police–citizen interactions. However, some felt they were singled out because of race and religion. Participants stated better police training in cultural competence would lead to greater police–citizen cooperation. All would contact police if the security of Canada were in danger. However, there are those who will never trust police.
Tackling radicalization and terrorism in Dutch mental health institutions: Outcomes of a Dutch population survey
Authors: Steinmetz Carl H.D.
Published: March 2021

Virtually no data are available on mental health institutions working on radicalization and terrorism. In the Netherlands we conducted a survey of all mental health institutions (n = 65) in 2016. Fifty-seven per cent responded. The result is that mental health institutions in the Netherlands have started to take small steps towards tacking radicalization and terrorism. These small steps, even by 2016, are a contrast to the reality of radicalization and terrorist incidents and attacks in the Netherlands since 2000. This outcome may have been caused by the resistance of Dutch psychiatrists in the mental health sector (often heard in the Greater Amsterdam region) to the idea that radicalisation and terrorist incidents and attacks are not their work either. For their view is, it is not our job if there is no DSM disorder.
The universal definition of myocardial infarction
Authors: Thygesen Kristian , Alpert Joseph S , Jaffe Allan S , White Harvey D
Published: March 2021

Myocardial infarction is defined by the presence of myocardial injury detected by abnormal cardiac biomarkers in the setting of acute clinical myocardial ischaemia. These conditions are met when there is a detection of a rise and/or fall of cardiac biomarkers, preferably cardiac troponins, with at least one value above the 99th percentile of the upper reference limit together with evidence of acute clinical myocardial ischaemia as recognized by at least one of the following: symptoms of ischaemia, ECG changes of new ischaemia, development of pathological Q waves, imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, or identification of an intracoronary thrombus by angiography or autopsy.
Mechanical complications of myocardial infarction
Authors: Puerto Elena , Bueno Héctor
Published: March 2021

Mechanical complications of acute myocardial infarction are those caused by ruptures or geometrical distortions of cardiac structures. Cardiac ruptures are currently rare complications, less than 1% in the era of reperfusion therapy, but often with catastrophic consequences, and include free wall rupture, the most frequent, interventricular septal rupture, and papillary muscle rupture. The clinical presentation may vary from unusually milder presentations to sudden presentation with severe hypotension, cardiogenic shock or electro-mechanical dissociation. Therefore, immediate diagnosis is key, generally by echocardiography, followed by resuscitation and/or hemodynamic support, pharmacological or mechanical. In the majority of cases, these complications require urgent surgical repair. In some cases percutaneous therapies may be a valid alternative. Mechanical complications due to geometrical distortion include functional ischemic mitral regurgitation, ventricular aneurysms and intraventricular thrombosis. These complications are more frequent than ruptures and, in general, less severe, ranging from accidental findings by imaging techniques in asymptomatic patients to advanced heart failure. Most often these complications can be treated medically and occasionally may need surgical therapy.
Implanted cardiac support devices
Authors: Morley-Smith Andrew C , Simon André R , Pepper John
Published: March 2021

Mechanical circulatory support forms a crucial and expanding element of advanced heart failure management. Short-term assistance is delivered in emergency situations or where the underlying condition is likely to quickly worsen, and these approaches are discussed in Chapter 30. This chapter focuses on implantable devices intended for the medium and long term. The first half of the chapter is aimed directly at practical clinical management, whilst the second half considers the evidence base for contemporary practice. The chapter concludes by considering new paradigms for implantable cardiac support. Most frequently, these devices support left ventricular function (left ventricular assist devices), and this comprises the majority of our discussion.
Pain in the intensive cardiovascular care unit
Authors: Jaggar Siân , Laycock Helen
Published: March 2021

Cardiac intensive care units admit a heterogeneous patient group Pain is common, occurring in up to 70% of medical and surgical patients Effective analgesia is important Pain is under-recognized and inadequately treated, particularly in medical patients Consequences of pain are widespread, involving multisystem physiological changes Pain causes significant psychological sequelae for patients, and ethical implications for physicians Pain management should utilize a systematic approach. Ensuring optimal patient comfort requires: Understanding of the potential causes of pain in cardiac intensive care Using validated pain assessment tools to identify the presence of pain and evaluate treatment effects Employing a multimodal, multidisciplinary management strategy
Perioperative management of the high-risk surgical patient: cardiac surgery
Authors: Ranucci Marco , Castelvecchio Serenella , Ballotta Andrea
Published: March 2021

During the last decade, as a result of continually improving surgical strategy and the technology which supports it (e.g. anaesthesia), cardiac surgery is offered to patients with advanced age and those with increasingly complex co-existing conditions that were previously considered to be contraindications. In addition, an increasing number of patients have previously undergone angioplasty, thereby delaying their initial coronary artery bypass graft surgery to a more advanced age. In general, candidates for cardiac surgery may now be not only older than in the past, but also more likely to have health problems such as hypertension and diabetes. Risk stratification may help to identify 'the' high-risk patient: 'pre-warned is pre-armed'. In high-risk cardiac surgery patients, the surgical treatment options and perioperative care must be tailored to each patient, in order to optimize the benefits and minimize the risk of detrimental effects. The preoperative anticoagulation practice is an important aspect, balancing the risk between ischaemic and bleeding complications. New antiplatelet agents and oral anticoagulants have been recently delivered, and their role in patients scheduled for heart surgery is an additional important issue.
BG Ind: the nearest doubly eclipsing, compact hierarchical quadruple system
Authors: Borkovits T , Rappaport S A , Maxted P F L , Terentev I , Omohundro M , Gagliano R , Jacobs T , Kristiansen M H , LaCourse D , Schwengeler H M , Vanderburg A , Blackford M G
Published: March 2021

BG Ind is a well-studied, bright, nearby binary consisting of a pair of F stars in a 1.46-d orbit. We have discovered in the TESS light curve for TIC 229804573 (aka BG Ind), a second eclipsing binary in the system with a 0.53-d period. Our subsequent analyses of the recent TESS and archival ground-based photometric and radial velocity (RV) data reveal that the two binaries are gravitationally bound in a 721-d period, moderately eccentric orbit. We present the results of a joint spectro-photodynamical analysis of the eclipse timing variation curves of both binaries based on TESS and ground-based archival data, the TESS light curve, archival RV data, and the spectral energy distribution, coupled with the use of PARSEC stellar isochrones. We confirm prior studies of BG Ind that found that the brighter binary A consists of slightly evolved F-type stars with refined masses of 1.32 and 1.43 M⊙, and radii of 1.59 and 2.34R⊙. The previously unknown binary B has two less massive stars of 0.69 and 0.64 M⊙ and radii of 0.64 and 0.61R⊙. Based on a number of different arguments that we discuss, we conclude that the three orbital planes are likely aligned to within 17○.
Observational properties of a general relativistic instability supernova from a primordial supermassive star
Authors: Moriya Takashi J , Chen Ke-Jung , Nakajima Kimihiko , Tominaga Nozomu , Blinnikov Sergei I
Published: March 2021

We present the expected observational properties of a general relativistic instability supernova (GRSN) from the 55 500 M⊙ primordial (Population III) star. Supermassive stars exceeding $10^4\, \mathrm{M}_\odot$ may exist in the early Universe. They are generally considered to collapse through the general relativistic instability to be seed black holes to form supermassive ($\sim 10^9\, \mathrm{M}_\odot$) black holes observed as high-redshift quasars. Some of them, however, may explode as GRSNe if the explosive helium burning unbinds the supermassive stars following the collapse triggered by the general relativistic instability. We perform the radiation hydrodynamics simulation of the GRSN starting shortly before the shock breakout. We find that the GRSN is characterized by a long-lasting (550 d) luminous ($1.5\times 10^{44}\, \mathrm{erg\, s^{-1}}$) plateau phase with the photospheric temperature of around 5000 K in the rest frame. The plateau phase lasts for decades when it appears at high redshifts and it will likely be observed as a persistent source in the future deep near-infrared imaging surveys. Especially, the near-infrared images reaching 29 AB magnitude that can be obtained by Galaxy and Reionization EXplorer (G-REX) and James Webb Space Telescope (JWST) allow us to identify GRSNe up to z ≃ 15. Deeper images enable us to discover GRSNe at even higher redshifts. Having extremely red colour, they can be distinguished from other persistent sources such as high-redshift galaxies by using colour information. We conclude that the deep near-infrared images are able to constrain the existence of GRSNe from the primordial supermassive stars in the Universe even without the time domain information.
Discovery of soft and hard X-ray time lags in low-mass AGNs
Authors: Mallick L , Wilkins D R , Alston W N , Markowitz A , De Marco B , Parker M L , Lohfink A M , Stalin C S
Published: March 2021

The scaling relations between the black hole (BH) mass and soft lag properties for both active galactic nuclei (AGNs) and BH X-ray binaries (BHXRBs) suggest the same underlying physical mechanism at work in accreting BH systems spanning a broad range of mass. However, the low-mass end of AGNs has never been explored in detail. In this work, we extend the existing scaling relations to lower mass AGNs, which serve as anchors between the normal-mass AGNs and BHXRBs. For this purpose, we construct a sample of low-mass AGNs ($M_{\rm BH}\lt 3\times 10^{6} \, \mathrm{M}_{\odot }$) from the XMM–Newton archive and measure frequency-resolved time-delays between the soft (0.3–1 keV) and hard (1–4 keV) X-ray emissions. We report that the soft band lags behind the hard band emission at high frequencies ∼[1.3−2.6] × 10−3 Hz, which is interpreted as a sign of reverberation from the inner accretion disc in response to the direct coronal emission. At low frequencies (∼[3−8] × 10−4 Hz), the hard-band lags behind the soft-band variations, which we explain in the context of the inward propagation of luminosity fluctuations through the corona. Assuming a lamppost geometry for the corona, we find that the X-ray source of the sample extends at an average height and radius of ∼10rg and ∼6rg, respectively. Our results confirm that the scaling relations between the BH mass and soft lag amplitude/frequency derived for higher mass AGNs can safely extrapolate to lower mass AGNs, and the accretion process is indeed independent of the BH mass.
ASASSN-18am/SN 2018gk: an overluminous Type IIb supernova from a massive progenitor
Authors: Bose Subhash , Dong Subo , Kochanek C S , Stritzinger M D , Ashall Chris , Benetti Stefano , Falco E , Filippenko Alexei V , Pastorello Andrea , Prieto Jose L , Somero Auni , Sukhbold Tuguldur , Zhang Junbo , Auchettl Katie , Brink Thomas G , Brown J S , Chen Ping , Fiore A , Grupe Dirk , Holoien T W-S , Lundqvist Peter , Mattila Seppo , Mutel Robert , Pooley David , Post R S , Reddy Naveen , Reynolds Thomas M , Shappee Benjamin J , Stanek K Z , Thompson Todd A , Villanueva S , Zheng WeiKang
Published: March 2021

ASASSN-18am/SN 2018gk is a newly discovered member of the rare group of luminous, hydrogen-rich supernovae (SNe) with a peak absolute magnitude of MV ≈ −20 mag that is in between normal core-collapse SNe and superluminous SNe. These SNe show no prominent spectroscopic signatures of ejecta interacting with circumstellar material (CSM), and their powering mechanism is debated. ASASSN-18am declines extremely rapidly for a Type II SN, with a photospheric-phase decline rate of ∼6.0 mag (100 d)−1. Owing to the weakening of H i and the appearance of He i in its later phases, ASASSN-18am is spectroscopically a Type IIb SN with a partially stripped envelope. However, its photometric and spectroscopic evolution shows significant differences from typical SNe IIb. Using a radiative diffusion model, we find that the light curve requires a high synthesized 56Ni mass $M_{\rm Ni} \sim 0.4\, \rm {M_{\odot }}$ and ejecta with high kinetic energy Ekin = (7–10) × 1051 erg. Introducing a magnetar central engine still requires $M_{\rm Ni} \sim 0.3\, \rm {M_{\odot }}$ and Ekin = 3 × 1051 erg. The high 56Ni mass is consistent with strong iron-group nebular lines in its spectra, which are also similar to several SNe Ic-BL with high 56Ni yields. The earliest spectrum shows ‘flash ionization’ features, from which we estimate a mass-loss rate of $\dot{M}\approx 2\times 10^{-4} \, \rm \rm {M_{\odot }}\,yr^{-1}$. This wind density is too low to power the luminous light curve by ejecta–CSM interaction. We measure expansion velocities as high as 17 000 $\rm {\, km\, s^{-1}}$ for Hα, which is remarkably high compared to other SNe II. We estimate an oxygen core mass of 1.8–3.4 M⊙ using the [O i] luminosity measured from a nebular-phase spectrum, implying a progenitor with a zero-age main-sequence mass of 19–26 M⊙.
Extensive Genome-Wide Phylogenetic Discordance Is Due to Incomplete Lineage Sorting and Not Ongoing Introgression in a Rapidly Radiated Bryophyte Genus
Authors: Meleshko Olena , Martin Michael D. , Korneliussen Thorfinn Sand , Schröck Christian , Lamkowski Paul , Schmutz Jeremy , Healey Adam , Piatkowski Bryan T. , Shaw A. Jonathan , Weston David J. , Flatberg Kjell Ivar , Szövényi Péter , Hassel Kristian , Stenøien Hans K.
Published: March 2021

The relative importance of introgression for diversification has long been a highly disputed topic in speciation research and remains an open question despite the great attention it has received over the past decade. Gene flow leaves traces in the genome similar to those created by incomplete lineage sorting (ILS), and identification and quantification of gene flow in the presence of ILS is challenging and requires knowledge about the true phylogenetic relationship among the species. We use whole nuclear, plastid, and organellar genomes from 12 species in the rapidly radiated, ecologically diverse, actively hybridizing genus of peatmoss (Sphagnum) to reconstruct the species phylogeny and quantify introgression using a suite of phylogenomic methods. We found extensive phylogenetic discordance among nuclear and organellar phylogenies, as well as across the nuclear genome and the nodes in the species tree, best explained by extensive ILS following the rapid radiation of the genus rather than by postspeciation introgression. Our analyses support the idea of ancient introgression among the ancestral lineages followed by ILS, whereas recent gene flow among the species is highly restricted despite widespread interspecific hybridization known in the group. Our results contribute to phylogenomic understanding of how speciation proceeds in rapidly radiated, actively hybridizing species groups, and demonstrate that employing a combination of diverse phylogenomic methods can facilitate untangling complex phylogenetic patterns created by ILS and introgression.
Barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel in situ analyses
Authors: Liu Songlei , Punthambaker Sukanya , Iyer Eswar P R , Ferrante Thomas , Goodwin Daniel , Fürth Daniel , Pawlowski Andrew C , Jindal Kunal , Tam Jenny M , Mifflin Lauren , Alon Shahar , Sinha Anubhav , Wassie Asmamaw T , Chen Fei , Cheng Anne , Willocq Valerie , Meyer Katharina , Ling King-Hwa , Camplisson Conor K , Kohman Richie E , Aach John , Lee Je Hyuk , Yankner Bruce A , Boyden Edward S , Church George M
Published: March 2021

We present barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel insitu analyses (BOLORAMIS), a reverse transcription-free method for spatially-resolved, targeted, in situ RNA identification of single or multiple targets. BOLORAMIS was demonstrated on a range of cell types and human cerebral organoids. Singleplex experiments to detect coding and non-coding RNAs in human iPSCs showed a stem-cell signature pattern. Specificity of BOLORAMIS was found to be 92% as illustrated by a clear distinction between human and mouse housekeeping genes in a co-culture system, as well as by recapitulation of subcellular localization of lncRNA MALAT1. Sensitivity of BOLORAMIS was quantified by comparing with single molecule FISH experiments and found to be 11%, 12% and 35% for GAPDH, TFRC and POLR2A, respectively. To demonstrate BOLORAMIS for multiplexed gene analysis, we targeted 96 mRNAs within a co-culture of iNGN neurons and HMC3 human microglial cells. We used fluorescence in situ sequencing to detect error-robust 8-base barcodes associated with each of these genes. We then used this data to uncover the spatial relationship among cells and transcripts by performing single-cell clustering and gene–gene proximity analyses. We anticipate the BOLORAMIS technology for in situ RNA detection to find applications in basic and translational research.
Oligomeric complexes formed by Redβ single strand annealing protein in its different DNA bound states
Authors: Caldwell Brian J , Norris Andrew , Zakharova Ekaterina , Smith Christopher E , Wheat Carter T , Choudhary Deepanshu , Sotomayor Marcos , Wysocki Vicki H , Bell Charles E
Published: March 2021

Redβ is a single strand annealing protein from bacteriophage λ that binds loosely to ssDNA, not at all to pre-formed dsDNA, but tightly to a duplex intermediate of annealing. As viewed by electron microscopy, Redβ forms oligomeric rings on ssDNA substrate, and helical filaments on the annealed duplex intermediate. However, it is not clear if these are the functional forms of the protein in vivo. We have used size-exclusion chromatography coupled with multi-angle light scattering, analytical ultracentrifugation and native mass spectrometry (nMS) to characterize the size of the oligomers formed by Redβ in its different DNA-bound states. The nMS data, which resolve species with the highest resolution, reveal that Redβ forms an oligomer of 12 subunits in the absence of DNA, complexes ranging from 4 to 14 subunits on 38-mer ssDNA, and a much more distinct and stable complex of 11 subunits on 38-mer annealed duplex. We also measure the concentration of Redβ in cells active for recombination and find it to range from 7 to 27 μM. Collectively, these data provide new insights into the dynamic nature of the complex on ssDNA, and the more stable and defined complex on annealed duplex.
Structural parameters of palindromic repeats determine the specificity of nuclease attack of secondary structures
Authors: Ait Saada Anissia , Costa Alex B , Sheng Ziwei , Guo Wenying , Haber James E , Lobachev Kirill S
Published: March 2021

Palindromic sequences are a potent source of chromosomal instability in many organisms and are implicated in the pathogenesis of human diseases. In this study, we investigate which nucleases are responsible for cleavage of the hairpin and cruciform structures and generation of double-strand breaks at inverted repeats in Saccharomyces cerevisiae. We demonstrate that the involvement of structure-specific nucleases in palindrome fragility depends on the distance between inverted repeats and their transcriptional status. The attack by the Mre11 complex is constrained to hairpins with loops <9 nucleotides. This restriction is alleviated upon RPA depletion, indicating that RPA controls the stability and/or formation of secondary structures otherwise responsible for replication fork stalling and DSB formation. Mus81-Mms4 cleavage of cruciforms occurs at divergently but not convergently transcribed or nontranscribed repeats. Our study also reveals the third pathway for fragility at perfect and quasi-palindromes, which involves cruciform resolution during the G2 phase of the cell cycle.
Single-molecule optical mapping of the distribution of DNA phosphorothioate epigenetics
Authors: Wei Yue , Huang Qinqin , Tian Xihao , Zhang Mingmin , He Junkai , Chen Xingxiang , Chen Chao , Deng Zixin , Li Zhiqiang , Chen Shi , Wang Lianrong
Published: March 2021

DNA phosphorothioate (PT) modifications, with the nonbridging phosphate oxygen replaced by sulfur, governed by DndABCDE or SspABCD, are widely distributed in prokaryotes and have a highly unusual feature of occupying only a small portion of available consensus sequences in a genome. Despite the presence of plentiful non-PT-protected consensuses, DNA PT modification is still employed as a recognition tag by the restriction cognate, for example, DndFGH or SspE, to discriminate and destroy PT-lacking foreign DNA. This raises a fundamental question about how PT modifications are distributed along DNA molecules to keep the restriction components in check. Here, we present two single-molecule strategies that take advantage of the nucleophilicity of PT in combination with fluorescent markers for optical mapping of both single- and double-stranded PT modifications across individual DNA molecules. Surprisingly, PT profiles vary markedly from molecule to molecule, with different PT locations and spacing distances between PT pairs, even in the presence of DndFGH or SspE. The results revealed unprecedented PT modification features previously obscured by ensemble averaging, providing novel insights into the riddles regarding unusual target selection by PT modification and restriction components.
Eggs as an affordable source of nutrients for adults and children living in food-insecure environments
Authors: Walker Sam , Baum J I
Published: March 2021

Food insecurity affects an estimated 12% of households in the United States. Adults and children who experience food insecurity are increased risk for development of metabolic diseases such as type 2 diabetes, obesity, and cardiovascular disease. The negative health outcomes associated with food insecurity are multifactorial; however, many of them may be caused by limited nutritional intake and poor diet quality. Dietary intake of eggs may be an applicable solution for food-insecure families who are challenged by limited nutritional intake. Eggs contain a variety of nutrients that support metabolic health. For instance, eggs are a complete source of high-quality protein and contain 16 vitamins and minerals. Furthermore, eggs are cost efficient. When comparing the relationship between foods on the basis of calories and unit cost, the energy cost of eggs is significantly less when compared with that of other animal-protein foods such as meat, poultry, and fish. However, dietary intake of eggs is controversial in regard to cardiovascular health. Thus, the aim of this review is to summarize the role of eggs in the diet and the impact eggs have on health for adults and children living in a food-insecure environment.
Multisectoral Approach on COVID-19 vaccination: a proposed solution on vaccine hesitancy
Authors: Corpuz Jeff Clyde G
Published: March 2021

As COVID-19 cases rise in one of Southeast Asia’s worst-hit nations, low public trust in vaccines will be a huge block in the government’s vaccination program. In a recent survey in January 2021 which was conducted by Pulse Asia, nearly half of Filipinos said that they would not get vaccinated against COVID-19 due to safety concerns. A proposed solution would be a Multisectoral Approach (MSA). MSA refers to the deliberate collaboration among various stakeholder groups (e.g. government, civil society and private and religious sectors) and sectors (e.g. health, environment and economy) to achieve a policy outcome. By engaging multiple sectors, such as interfaith collaborations, governments can leverage knowledge, expertise, reach and resources, benefiting from their combined and varied strengths as they work toward the shared goal of building public trust on vaccines.
Second-Generation Antipsychotic Use in Pediatric Emergency Medicine
Authors: Lambert Clare , Panagiotopoulos Constadina , Davidson Jana , Goldman Ran D.
Published: March 2021

In recent years, the number of patients presenting to the emergency department with mental health complaints has been growing, alongside an increase in second-generation antipsychotic (SGAs) prescriptions for a variety of mental health conditions. Children treated with SGAs may have abnormalities, such as rapid weight gain and central adiposity, glucose intolerance, dyslipidemia, and hypertension; they may present to the pediatric emergency department with components of metabolic syndrome or type 2 diabetes, and a subsequent significant risk for cardiovascular complications later in life. Pediatric emergency department providers may serve as a safety net for patients to detect SGA-related metabolic complications, especially among vulnerable populations lacking access to primary care or psychiatric services.
Renewable Energy Use in Australian Public Hospitals
Authors: Burch Hayden , Anstey Matthew , McGain Forbes
Published: March 2021

Objective

Are Australian hospitals moving towards renewable energy sources for
their electricity, and aligning energy choices with core business, i.e.
protecting and promoting health?

Design

Cross-sectional analysis of Australian state/territory amalgamated
energy data

Setting

Healthcare’s carbon footprint is approximately 7% of Australia’s total
carbon footprint. It is unknown if Australian public hospitals are
decoupling energy needs from carbon emissions over and above state/territory
based renewable energy targets.

Participants

693 Australian public hospitals direct energy usage (renewable &
non-renewable electricity [produced/purchased], natural gas, liquefied
petroleum gas, for the three consecutive years from 2016/17 to
2018/19.

Main outcome measures

All direct energy produced/purchased and consumed (converted to
kilowatt-hours).

Results

Australian public hospitals consumed 4,122 gigawatt-hours of energy in
2018/19. Electricity use was 2,504 (61%) GWh, natural gas 1,436 (35%) GWh
and renewable energy 94 GWh (2.3%). Victoria and New South Wales combined
consumed 2,494/ 4,122 GWh (60%) of total Australian public healthcare energy
but each produced/purchased less than 1% renewable electricity. For
Queensland, a Health GreenPower purchase comprised the majority (71/94 GWh;
76%) of renewable energy production/purchase by all Australian public
hospitals. By comparison, individual tertiary education institutions
produced/purchased more renewable energy than all Australian public
hospitals combined (University of NSW 124 GWh/yr, Swinburne University 90
GWh/yr, 2018/19).

Conclusions

Australian public hospitals obtain approximately 2.3% of total energy
from renewable electricity. One third of hospital energy use stems from
fossil gas use. The Australian public hospital system has no documented
plans to transition to renewable energy, contrasting with the University
sector.

The known

Australian healthcare contributes approximately 7% of
Australia’s total carbon footprint with public hospital energy use a
major source of healthcare associated carbon emissions.

The new

Australian public hospitals consumed 4122 gigawatt-hours in
2018/2019. Approximately 2.3% (94/4,122 gigawatt-hours) of hospital
energy was sourced from renewables, beyond state-wide renewable
electricity penetration.

The implications

Australian public hospitals are large emitters of greenhouse
gases. Hospital fossil fuel energy use and subsequent pollution
continues unabated. Such increasing pollution is at odds with the
ethos ‘first do no harm’.
Autoantibodies against nephrin elucidate a novel autoimmune phenomenon in proteinuric kidney disease
Authors: Watts Andrew J.B. , Keller Keith H. , Lerner Gabriel , Rosales Ivy , Collins A. Bernard , Sekulic Miroslav , Waikar Sushrut S. , Chandraker Anil , Riella Leonardo V. , Alexander Mariam P. , Troost Jonathan P. , Chen Junbo , Fermin Damian , Yee Jennifer Lai , Sampson Matthew , Beck Laurence H. , Henderson Joel M. , Greka Anna , Rennke Helmut G. , Weins Astrid
Published: March 2021

Dysfunction of podocytes, cells critical for glomerular filtration, underlies proteinuria and kidney failure. Genetic forms of proteinuric kidney disease can be caused by mutations in several podocyte genes, including nephrin, a critical component of the kidney filter. In contrast, the etiology of acquired acute-onset nephrotic syndrome has remained elusive. Here we identify autoantibodies against nephrin in serum and glomeruli of a subset of adults and children with non-congenital acute nephrotic syndrome. Our findings align with published experimental animal studies and elucidate a novel autoimmune phenomenon in proteinuric kidney disease interfering with glomerular filter integrity.
The kidney releases a non-polymerizing form of Uromodulin in the urine and circulation that retains the external hydrophobic patch domain
Authors: Micanovic Radmila , LaFavers Kaice A. , Patidar Kavish R. , Ghabril Marwan S. , Doud Emma H. , Mosley Amber L. , Sabo Angela R. , Khan Shehnaz , El-Achkar Tarek M.
Published: March 2021

Uromodulin (Tamm-Horsfall protein, THP) is a glycoprotein uniquely produced in the kidney. It is released by cells of the thick ascending limbs (TAL) apically in the urine, and basolaterally in the renal interstitium and systemic circulation. Processing of mature urinary THP, which polymerizes into supra-molecular filaments, requires cleavage of an external hydrophobic patch (EHP) at the C terminus. However, THP in the circulation is not polymerized, and it remains unclear if non-aggregated forms of THP exist natively in the urine. We propose that an alternative processing path, which retains the EHP domain, can lead to a non-polymerizing form of THP. We generated an antibody that specifically recognizes THP with retained EHP (THP+EHP) and established its presence in the urine in a non-polymerized native state. Proteomic characterization of urinary THP+EHP revealed its C-terminus to end at F617. In the human kidney, THP+EHP was not only detected in TAL cells, but also diffusely in the renal parenchyma. Using immunoprecipitation followed by proteomic sequencing and immunoblotting, we then demonstrated that serum THP has also retained EHP. In a small cohort of patients at risk for acute kidney injury (AKI), admission urinary THP+EHP was significantly lower in patients who subsequently developed AKI during hospitalization. Our findings uncover novel insights into uromodulin biology by establishing the presence of an alternative path for cellular processing, which could explain the release of non-polymerizing THP in the circulation. Larger studies are needed to establish the utility of urinary THP+EHP as a sensitive biomarker of kidney health and susceptibility to injury.
A Systematic Review and Meta-Analysis on Catastrophic Cost incurred by Tuberculosis Patients and their Households
Authors: Ghazy Ramy Mohamed , Saeh Haider M. El , Abdulaziz Shaimaa , Hammouda Esraa Abdellatif , Elzorkany Amira , Kheder Heba , Zarif Nardine , Elrewany Ehab , ElHafeez Samar Abd
Published: March 2021

Background

As one of the World Health Organization (WHO) End Tuberculosis (TB) Strategy is to reduce the proportion of TB affected families that face catastrophic costs to 0% by 2020. This systematic review and meta-analysis aimed to estimate the pooled proportion of TB affected households who face catastrophic cost.

Method

A search of the online database through September 2020 was performed. A total of 5114 articles were found, of which 29 articles got included in quantitative synthesis. Catastrophic cost is defined if total cost related to TB exceeded 20% of annual pre-TB household income. R software was used to estimate the pooled proportion at 95% confidence intervals (CIs) using the fixed/random-effect models.

Result

The proportion of patients faced catastrophic cost was 43% (95% CI 34-52, I2= 99%); 32% (95% CI 29 – 35, I2= 70%) among drug sensitive, and 80% (95% CI 74-85, I2= 54%) among drug resistant, and 81% (95%CI 78-84%, I2= 0%) among HIV patients. Regarding active versus passive case finding the pooled proportion of catastrophic cost was 12% (95% CI 9-16, I2= 95%) versus 42% (95% CI 35-50, I2= 94%). The pooled proportion of direct cost to the total cost was 45% (95% CI 39-51, I2= 91%). The pooled proportion of patients facing catastrophic health expenditure (CHE) at cut of point of 10% of their yearly income was 45% (95% CI 35-56, I2= 93%) while at 40% of their capacity to pay was 63% (95% CI 40-80, I2= 96%).

Conclusion

Despite the ongoing efforts, there is a significant proportion of patients facing catastrophic cost, which represent a main obstacle against TB control.

PROSPERO registration

CRD42020221283
Prediction of intensive care unit mortality based on missing events
Authors: Shoji Tatsuma , Yonekura Hiroshi , Yoshiharu Sato , Kawasaki Yohei
Published: March 2021

Background

The increasing availability of electronic health records has made it possible to construct and implement models for predicting intensive care unit (ICU) mortality using machine learning. However, the algorithms used are not clearly described, and the performance of the model remains low owing to several missing values, which is unavoidable in big databases.

Methods

We developed an algorithm for subgrouping patients based on missing event patterns using the Philips eICU Research Institute (eRI) database as an example. The eRI database contains data associated with 200,859 ICU admissions from many hospitals (>400) and is freely available. We then constructed a model for each subgroup using random forest classifiers and integrated the models. Finally, we compared the performance of the integrated model with the Acute Physiology and Chronic Health Evaluation (APACHE) scoring system, one of the best known predictors of patient mortality, and the imputation approach-based model.

Results

Subgrouping and patient mortality prediction were separately performed on two groups: the sepsis group (the ICU admission diagnosis of which is sepsis) and the non-sepsis group (a complementary subset of the sepsis group). The subgrouping algorithm identified a unique, clinically interpretable missing event patterns and divided the sepsis and non-sepsis groups into five and seven subgroups, respectively. The integrated model, which comprises five models for the sepsis group or seven models for the non-sepsis group, greatly outperformed the APACHE IV or IVa, with an area under the receiver operating characteristic (AUROC) of 0.91 (95% confidence interval 0.89–0.92) compared with 0.79 (0.76–0.81) for the APACHE system in the sepsis group and an AUROC of 0.90 (0.89–0.91) compared with 0.86 (0.85–0.87) in the non-sepsis group. Moreover, our model outperformed the imputation approach-based model, which had an AUROC of 0.85 (0.83–0.87) and 0.87 (0.86–0.88) in the sepsis and non-sepsis groups, respectively.

Conclusions

We developed a method to predict patient mortality based on missing event patterns. Our method more accurately predicts patient mortality than others. Our results indicate that subgrouping, based on missing event patterns, instead of imputation is essential and effective for machine learning against patient heterogeneity.

Trial registration

Not applicable.
Novel clinical subphenotypes in COVID-19: derivation, validation, prediction, temporal patterns, and interaction with social determinants of health
Authors: Su Chang , Zhang Yongkang , Flory James H , Weiner Mark G. , Kaushal Rainu , Schenck Edward J. , Wang Fei
Published: March 2021

The coronavirus disease 2019 (COVID-19) is heterogeneous and our understanding of the biological mechanisms of host response to the novel viral infection remains limited. Identification of meaningful clinical subphenotypes may benefit pathophysiological study, clinical practice, and clinical trials. Here, our aim was to derive and validate COVID-19 subphenotypes using machine learning and routinely collected clinical data, assess temporal patterns of these subphenotypes during the pandemic course, and examine their interaction with social determinants of health (SDoH). We retrospectively analyzed 14418 COVID-19 patients in five major medical centers in New York City (NYC), between March 1 and June 12, 2020. Using clustering analysis, four biologically distinct subphenotypes were derived in the development cohort (N = 8199). Importantly, the identified subphenotypes were highly predictive of clinical outcomes (especially 60-day mortality). Sensitivity analyses in the development cohort, and re-derivation and prediction in the internal (N = 3519) and external (N = 3519) validation cohorts confirmed the reproducibility and usability of the subphenotypes. Further analyses showed varying subphenotype prevalence across the peak of the outbreak in NYC. We also found that SDoH specifically influenced mortality outcome in Subphenotype IV, which is associated with older age, worse clinical manifestation, and high comorbidity burden. Our findings may lead to a better understanding of how COVID-19 causes disease in different populations and potentially benefit clinical trial development. The temporal patterns and SDoH implications of the subphenotypes may add new insights to health policy to reduce social disparity in the pandemic.
Calling differential DNA methylation at cell-type resolution: avoiding misconceptions and promoting best practices
Authors: Jing Han , Zheng Shijie C. , Breeze Charles E. , Beck Stephan , Teschendorff Andrew E.
Published: March 2021

The accurate detection of cell-type specific DNA methylation alterations in the context of general epigenome studies is an important task to improve our understanding of epigenomics in disease development. Although a number of statistical algorithms designed to address this problem have emerged, the task remains challenging. Here we show that a recent commentary by Rahmani et al, that aims to address misconceptions and best practices in the field, continues to suffer from critical misconceptions in how statistical algorithms should be compared and evaluated. In addition, we report contradictory results on real EWAS datasets.
Sex-specific DNA methylation changes in Alzheimer’s disease pathology
Authors: Zhang Lanyu , Young Juan I. , Gomez Lissette , Silva Tiago C. , Schmidt Michael A. , Cai Jesse , Chen Xi , Martin Eden R. , Wang Lily
Published: March 2021

Sex is an important factor that contributes to the clinical and biological heterogeneities in Alzheimer’s disease (AD), but the regulatory mechanisms underlying sex disparity in AD are still not well understood. DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD. We performed the first large-scale sex-specific meta-analysis of DNA methylation changes in AD, by re-analyzing four recent epigenome-wide association studies totaling more than 1000 postmortem prefrontal cortex brain samples using a uniform analytical pipeline. For each cohort we employed two complementary analytical strategies, a sex-stratified analysis that examined methylation-Braak stage associations in male and female samples separately, and a sex-by-Braak stage interaction analysis that compared the magnitude of these associations between different sexes. Our analysis uncovered 14 novel CpGs, mapped to genes such asTMEM39AandTNXBthat are associated with AD in a sex-specific manner.TMEM39Ais known to be involved in inflammation, dysregulated type I interferon responses, and other immune processes.TNXBencodes tenascin proteins, which are extracellular matrix glycoproteins demonstrated to modulate synaptic plasticity in the brain. Moreover, for many previously implicated AD genes, such asMBPandAZU1, our analysis provided the new insights that they were predominately driven by effects in only one sex. These sex-specific DNA methylation changes were enriched in divergent biological processes such as integrin activation in females and complement activation in males. Importantly, a number of drugs commonly prescribed for AD patients also targeted these genes with sex-specific DNA methylation changes. Our study implicated multiple new loci and biological processes that affected AD in a sex-specific manner and highlighted the importance of sex-specific treatment regimens for AD patients.
The Socioeconomic Gradient in Epigenetic Aging Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study
Authors: Schmitz Lauren L. , Zhao Wei , Ratliff Scott M. , Goodwin Julia , Miao Jiacheng , Lu Qiongshi , Guo Xiuqing , Taylor Kent D. , Ding Jingzhong , Liu Yongmei , Levine Morgan , Smith Jennifer A.
Published: March 2021

Epigenetic clocks have been widely used to predict disease risk in multiple tissues or cells. Their success as a measure of biological aging has prompted research on the connection between epigenetic pathways of aging and the socioeconomic gradient in health and mortality. However, studies examining social correlates of epigenetic aging have yielded inconsistent results. We conducted a comprehensive, comparative analysis of associations between various dimensions of socioeconomic status (SES) (education, income, wealth, occupation, neighborhood environment, and childhood SES) and eight epigenetic clocks in two large U.S. aging studies: The Multi-Ethnic Study of Atherosclerosis (MESA) (n=1,211) and the Health and Retirement Study (HRS) (n=4,018). In both studies, we found robust associations between SES measures in adulthood and the GrimAge and DunedinPoAm clocks (Bonferroni corrected p-value<0.01). In the HRS, significant associations with the Levine and Yang clocks are also evident. These associations are only partially mediated by smoking, alcohol consumption, and obesity, which suggests that differences in health behaviors alone cannot explain the SES gradient in epigenetic aging. Further analyses revealed concurrent associations between polygenic risk for accelerated intrinsic epigenetic aging, SES, and the Levine clock, indicating that genetic predisposition and social disadvantage may contribute independently to faster epigenetic aging.