bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipidomics of homeoviscous adaptation to low temperatures in
Staphylococcus aureus
utilizing exogenous straight-chain unsaturated fatty acids
Authors: Barbarek Shannon C. , Shah Ritika , Paul Sharanya , Alvarado Gloria , Appala Keerthi , Phillips Caiden , Henderson Emma C. , Strandquist Evan T. , Pokorny Antje , Singh Vineet K. , Gatto Craig , Dahl Jan-Ulrik , Hines Kelly M. , Wilkinson Brian J.
Published: July 2024

It is well established that
Staphylococcus aureus
can incorporate exogenous straight-chain unsaturated fatty acids (SCUFAs) into membrane phospho- and glyco-lipids from various sources in supplemented culture media and when growing
in vivo
during infection. Given the enhancement of membrane fluidity when oleic acid (C18:1Δ9) is incorporated into lipids, we were prompted to examine the effect of medium supplementation with C18:1Δ9 on growth at low temperatures. C18:1Δ9 supported the growth of a cold-sensitive, branched-chain fatty acid (BCFA)-deficient mutant at 12°C. Interestingly, we found similar results in the BCFA-sufficient parental strain, supported by the fact that the incorporation of C18:1Δ9 into the membrane increased membrane fluidity in both strains. We show that the incorporation of C18:1Δ9 and its elongation product C20:1Δ11 into membrane lipids was required for growth stimulation and relied on a functional FakAB incorporation system. Lipidomics analysis of the phosphatidylglycerol and diglycosyldiacylglycerol lipid classes revealed major impacts of C18:1Δ9 and temperature on lipid species. Growth at 12°C in the presence of C18:1Δ9 also led to increased production of the carotenoid pigment staphyloxanthin. The enhancement of growth by C18:1Δ9 is an example of homeoviscous adaptation to low temperatures utilizing an exogenous fatty acid. This may be significant in the growth of
S. aureus
at low temperatures in foods that commonly contain C18:1Δ9 and other SCUFAs in various forms.

IMPORTANCE

We show that
Staphylococcus aureus
can use its known ability to incorporate exogenous fatty acids to enhance its growth at low temperatures. Individual species of phosphatidylglycerols and diglycosyldiacylglycerols bearing one or two degrees of unsaturation derived from the incorporation of C18:1Δ9 at 12°C are described for the first time. In addition, enhanced production of the carotenoid staphyloxanthin occurs at low temperatures. The studies describe a biochemical reality underlying membrane biophysics. This is an example of homeoviscous adaptation to low temperatures utilizing exogenous fatty acids over the regulation of the biosynthesis of endogenous fatty acids. The studies have likely relevance to food safety in that unsaturated fatty acids may enhance the growth of
S. aureus
in the food environment.
Identification of the proteolytic signature in CVB3-infected cells
Authors: Vlok Marli , Solis Nestor , Sadasivan Jibin , Mohamud Yasir , Warsaba Reid , Kizhakkedathu Jayachandran , Luo Honglin , Overall Christopher M. , Jan Eric
Published: July 2024

Coxsackievirus B3 (CVB3) encodes proteinases that are essential for processing of the translated viral polyprotein. Viral proteinases also target host proteins to manipulate cellular processes and evade innate antiviral responses to promote replication and infection. While some host protein substrates of the CVB3 3C and 2A cysteine proteinases have been identified, the full repertoire of targets is not known. Here, we utilize an unbiased quantitative proteomics-based approach termed terminal amine isotopic labeling of substrates (TAILS) to conduct a global analysis of CVB3 protease-generated N-terminal peptides in both human HeLa and mouse cardiomyocyte (HL-1) cell lines infected with CVB3. We identified >800 proteins that are cleaved in CVB3-infected HeLa and HL-1 cells including the viral polyprotein, known substrates of viral 3C proteinase such as PABP, DDX58, and HNRNPs M, K, and D and novel cellular proteins. Network and GO-term analysis showed an enrichment in biological processes including immune response and activation, RNA processing, and lipid metabolism. We validated a subset of candidate substrates that are cleaved under CVB3 infection and some are direct targets of 3C proteinase
in vitro
. Moreover, depletion of a subset of TAILS-identified target proteins decreased viral yield. Characterization of two target proteins showed that expression of 3C
pro
-targeted cleaved fragments of emerin and aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 modulated autophagy and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, respectively. The comprehensive identification of host proteins targeted during virus infection provides insights into the cellular pathways manipulated to facilitate infection.

IMPORTANCE

RNA viruses encode proteases that are responsible for processing viral proteins into their mature form. Viral proteases also target and cleave host cellular proteins; however, the full catalog of these target proteins is incomplete. We use a technique called terminal amine isotopic labeling of substrates (TAILS), an N-terminomics to identify host proteins that are cleaved under virus infection. We identify hundreds of cellular proteins that are cleaved under infection, some of which are targeted directly by viral protease. Revealing these target proteins provides insights into the host cellular pathways and antiviral signaling factors that are modulated to promote virus infection and potentially leading to virus-induced pathogenesis.
Comprehensive proteomic analysis of HCoV-OC43 virions and virus-modulated extracellular vesicles
Authors: Joharinia Negar , Bonneil Éric , Grandvaux Nathalie , Thibault Pierre , Lippé Roger
Published: July 2024

Viruses are obligate parasites that depend on the cellular machinery for their propagation. Several viruses also incorporate cellular proteins that facilitate viral spread. Defining these cellular proteins is critical to decipher viral life cycles and delineate novel therapeutic strategies. While numerous studies have explored the importance of host proteins in coronavirus spread, information about their presence in mature virions is limited. In this study, we developed a protocol to highly enrich mature HCoV-OC43 virions and characterize them by proteomics. Recognizing that cells release extracellular vesicles whose content is modulated by viruses, and given our ability to separate virions from these vesicles, we also analyzed their protein content in both uninfected and infected cells. We uncovered 69 unique cellular proteins associated with virions including 31 high-confidence hits. These proteins primarily regulate RNA metabolism, enzymatic activities, vesicular transport, cell adhesion, metabolite interconversion, and translation. We further discovered that the virus had a profound impact on exosome composition, incorporating 47 novel cellular proteins (11 high confidence) and excluding 92 others (61 high confidence) in virus-associated extracellular vesicles compared to uninfected cells. Moreover, a dsiRNA screen revealed that 11 of 18 select targets significantly impacted viral yields, including proteins found in virions or extracellular vesicles. Overall, this study provides new and important insights into the incorporation of numerous host proteins into HCoV-OC43 virions, their biological significance, and the ability of the virus to modulate extracellular vesicles.

IMPORTANCE

In recent years, coronaviruses have dominated global attention, making it crucial to develop methods to control them and prevent future pandemics. Besides viral proteins, host proteins play a significant role in viral propagation and offer potential therapeutic targets. Targeting host proteins is advantageous because they are less likely to mutate and develop resistance compared to viral proteins, a common issue with many antiviral treatments. In this study, we examined the protein content of the less virulent biosafety level 2 HCoV-OC43 virus as a stand-in for the more virulent SARS-CoV-2. Our findings reveal that several cellular proteins incorporated into the virion regulate viral spread. In addition, we report that the virus extensively modulates the content of extracellular vesicles, enhancing viral dissemination. This underscores the critical interplay between the virus, host proteins, and extracellular vesicles.
Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission
Authors: Benlarbi Mehdi , Ding Shilei , Bélanger Étienne , Tauzin Alexandra , Poujol Raphaël , Medjahed Halima , El Ferri Omar , Bo Yuxia , Bourassa Catherine , Hussin Julie , Fafard Judith , Pazgier Marzena , Levade Inès , Abrams Cameron , Côté Marceline , Finzi Andrés
Published: July 2024

The continued evolution of severe acute respiratory syndrome 2 (SARS-CoV-2) requires persistent monitoring of its subvariants. Omicron subvariants are responsible for the vast majority of SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% of circulating strains as of January 2024. To better understand parameters involved in viral transmission, we characterized the functional properties of Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3, BA.2.86 and JN.1. We tested their capacity to evade plasma-mediated recognition and neutralization, binding to angiotensin-converting enzyme 2 (ACE2), their susceptibility to cold inactivation, Spike processing, as well as the impact of temperature on Spike-ACE2 interaction. We found that compared to the early wild-type (D614G) strain, most Omicron subvariants' Spike glycoproteins evolved to escape recognition and neutralization by plasma from individuals who received a fifth dose of bivalent (BA.1 or BA.4/5) mRNA vaccine and improve ACE2 binding, particularly at low temperatures. Moreover, BA.2.86 had the best affinity for ACE2 at all temperatures tested. We found that Omicron subvariants’ Spike processing is associated with their susceptibility to cold inactivation. Intriguingly, we found that Spike-ACE2 binding at low temperature was significantly associated with growth rates of Omicron subvariants in humans. Overall, we report that Spikes from newly emerged Omicron subvariants are relatively more stable and resistant to plasma-mediated neutralization, present improved affinity for ACE2 which is associated, particularly at low temperatures, with their growth rates.

IMPORTANCE

The persistent evolution of SARS-CoV-2 gave rise to a wide range of variants harboring new mutations in their Spike glycoproteins. Several factors have been associated with viral transmission and fitness such as plasma-neutralization escape and ACE2 interaction. To better understand whether additional factors could be of importance in SARS-CoV-2 variants’ transmission, we characterize the functional properties of Spike glycoproteins from several Omicron subvariants. We found that the Spike glycoprotein of Omicron subvariants presents an improved escape from plasma-mediated recognition and neutralization, Spike processing, and ACE2 binding which was further improved at low temperature. Intriguingly, Spike-ACE2 interaction at low temperature is strongly associated with viral growth rate, as such, low temperatures could represent another parameter affecting viral transmission.
Exploring Barmah Forest virus pathogenesis: molecular tools to investigate non-structural protein 3 nuclear localization and viral genomic determinants of replication
Authors: Omler Ailar , Mutso Margit , Vaher Mihkel , Freitas Joseph R. , Taylor Adam , David Cassandra T. , Moseley Gregory W. , Liu Xiang , Merits Andres , Mahalingam Suresh
Published: July 2024

Barmah Forest virus (BFV) is a mosquito-borne virus that causes arthralgia with accompanying rash, fever, and myalgia in humans. The virus is mainly found in Australia and has caused outbreaks associated with significant health concerns. As the sole representative of the Barmah Forest complex within the genus
Alphavirus
, BFV is not closely related genetically to other alphaviruses. Notably, basic knowledge of BFV molecular virology has not been well studied due to a lack of critical investigative tools such as an infectious clone. Here we describe the construction of an infectious BFV cDNA clone based on Genbank sequence and demonstrate that the clone-derived virus has
in vitro
and
in vivo
properties similar to naturally occurring virus, BFV field isolate 2193 (BFV2193-FI). A substitution in nsP4, V1911D, which was identified in the Genbank reference sequence, was found to inhibit virus rescue and replication. T1325P substitution in nsP2 selected during virus passaging was shown to be an adaptive mutation, compensating for the inhibitory effect of nsP4-V1911D. The two mutations were associated with changes in viral non-structural polyprotein processing and type I interferon (IFN) induction. Interestingly, a nuclear localization signal, active in mammalian but not mosquito cells, was identified in nsP3. A point mutation abolishing nsP3 nuclear localization attenuated BFV replication. This effect was more prominent in the presence of type I interferon signaling, suggesting nsP3 nuclear localization might be associated with IFN antagonism. Furthermore, abolishing nsP3 nuclear localization reduced virus replication in mice but did not significantly affect disease.

IMPORTANCE

Barmah Forest virus (BFV) is Australia’s second most prevalent arbovirus, with approximately 1,000 cases reported annually. The clinical symptoms of BFV infection include rash, polyarthritis, arthralgia, and myalgia. As BFV is not closely related to other pathogenic alphaviruses or well-studied model viruses, our understanding of its molecular virology and mechanisms of pathogenesis is limited. There is also a lack of molecular tools essential for corresponding studies. Here we describe the construction of an infectious clone of BFV, variants harboring point mutations, and sequences encoding marker protein. In infected mammalian cells, nsP3 of BFV was located in the nuclei. This finding extends our understanding of the diverse mechanisms used by alphavirus replicase proteins to interact with host cells. Our novel observations highlight the complex synergy through which the viral replication machinery evolves to correct mutation errors within the viral genome.
Mucin-induced surface dispersal of
Staphylococcus aureus
and
Staphylococcus epidermidis
via quorum-sensing dependent and independent mechanisms
Authors: Jacob Kristin M. , Hernández-Villamizar Santiago , Hammer Neal D. , Reguera Gemma
Published: July 2024

Nasopharyngeal carriage of staphylococci spreads potentially pathogenic strains into (peri)oral regions and increases the chance of cross-infections. Some laboratory strains can also move rapidly on hydrated agar surfaces, but the biological relevance of these observations is not clear. Using soft-agar [0.3% (wt/vol)] plate assays, we demonstrate the rapid surface dispersal of (peri)oral isolates of
Staphylococcus aureus
and
Staphylococcus epidermidis
and closely related laboratory strains in the presence of mucin glycoproteins. Mucin-induced dispersal was a stepwise process initiated by the passive spreading of the growing colonies followed by their rapid branching (dendrites) from the colony edge. Although most spreading strains used mucin as a growth substrate, dispersal was primarily dependent on the lubricating and hydrating properties of the mucins. Using
S. aureus
JE2 as a genetically tractable representative, we demonstrate that mucin-induced dendritic dispersal, but not colony spreading, is facilitated by the secretion of surfactant-active phenol-soluble modulins (PSMs) in a process regulated by the
agr
quorum-sensing system. Furthermore, the dendritic dispersal of
S. aureus
JE2 colonies was further stimulated in the presence of surfactant-active supernatants recovered from the most robust (peri)oral spreaders of
S. aureus
and
S. epidermidis
. These findings suggest complementary roles for lubricating mucins and staphylococcal PSMs in the active dispersal of potentially pathogenic strains from perioral to respiratory mucosae, where gel-forming, hydrating mucins abound. They also highlight the impact that interspecies interactions have on the co-dispersal of
S. aureus
with other perioral bacteria, heightening the risk of polymicrobial infections and the severity of the clinical outcomes.

IMPORTANCE

Despite lacking classical motility machinery, nasopharyngeal staphylococci spread rapidly in (peri)oral and respiratory mucosa and cause cross-infections. We describe laboratory conditions for the reproducible study of staphylococcal dispersal on mucosa-like surfaces and the identification of two dispersal stages (colony spreading and dendritic expansion) stimulated by mucin glycoproteins. The mucin type mattered as dispersal required the surfactant activity and hydration provided by some mucin glycoproteins. While colony spreading was a passive mode of dispersal lubricated by the mucins, the more rapid and invasive form of dendritic expansion of
Staphylococcus aureus
and
Staphylococcus epidermidis
required additional lubrication by surfactant-active peptides (phenol-soluble modulins) secreted at high cell densities through quorum sensing. These results highlight a hitherto unknown role for gel-forming mucins in the dispersal of staphylococcal strains associated with cross-infections and point at perioral regions as overlooked sources of carriage and infection by staphylococci.
Third-Harmonic Generation in Plasmonic Metasurfaces Fabricated by Direct Femtosecond Laser Printing
Authors: Pavlov D. V. , Cherepakhin A. B. , Zhizhchenko A. Yu. , Sergeev A. A. , Mitsai E. V. , Kuchmizhak A. A. , Kudryashov S. I.
Published: July 2024

Direct ablation-free femtosecond laser printing has been used to fabricate a metasurface in the form of ordered arrays of hollow nanobumps on the surface of a thin gold film. Resonant dips in the reflection spectra of fabricated metasurfaces, as well as a resonant increase in the third-harmonic intensity by two orders of magnitude, at the spectral matching of the observed optical resonances of the structure and the pump wavelength of the fundamental harmonic indicate that such ordered nanostructures allows the existence of high-Q-factor collective plasmon resonances, which are associated with the excitation and destructive interference of plasmon-polariton waves.
Structural and Magnetic Transformations from CuCl to Cu2Cl(OH)3 Induced by H2O and CuCl2
Authors: Pimentel D. P.
Published: July 2024

This study explores the oxidation dynamics of “pure” CuCl during prolonged environmental exposure through X-ray diffraction and temperature-dependent magnetization assessments. While CuCl is traditionally considered diamagnetic, our investigation reveals the emergence of an antiferromagnetic transition at 4.7 K. This anomaly is potentially induced by the integration of water molecules into the CuCl matrix. The hydration process initiates a series of oxidation reactions, ultimately transmuting CuCl into Cu2Cl(OH)3. Over time, the distinctive diffraction pattern peaks corresponding to CuCl diminish, concurrently with the appearance and intensification of those ascribed to Cu2Cl(OH)3, culminating in a complete phase transition as confirmed by X-ray analysis. Correspondingly, magnetization measurements clearly discern magnetic transitions at 6.4 and 16 K, intensifying with the sample’s exposure duration. These findings illuminate the stark potential for probing the magnetic intricacies of Cu2Cl(OH)3, a subject that remains a compelling and unresolved intrigue within the field.
Carcinoma ex-pleomorphic adenoma of parotid gland presenting as a gigantic cervicofacial mass
Authors: Mehra Bhupendra , Ghoshal Soumya , Dubhashi Siddharth P , Fulmali Ateet
Published: July 2024

When neglected for a long time, salivary gland pleomorphic adenoma (PA) can attain a considerable size, increasing the patient’s morbidity along with the risk of malignant transformation. Very few case reports are available describing PA of the parotid glands presenting as a large cervicofacial mass. We report a case of epithelial myoepithelial carcinoma —a rare subtype of carcinoma ex-PA (Ca-Ex-PA) of non-luminal differentiation, that developed over a long period in a primary PA of the parotid gland and presented as a giant cervicofacial mass.
Environmental challenges facing athletes, stakeholders and spectators at Paris 2024 Olympic and Paralympic Games: an evidence-based review of mitigation strategies and recommendations
Authors: Mougin Loïs , Bougault Valérie , Racinais Sébastien , Mountjoy Margo L , Stephenson Ben , Carter Sarah , James Lewis J , Mears Stephen A , Taylor Lee
Published: July 2024

The upcoming Paris 2024 Olympic and Paralympic Games could face environmental challenges related to heat, air quality and water quality. These challenges will pose potential threats to athletes and impact thousands of stakeholders and millions of spectators. Recognising the multifaceted nature of these challenges, a range of strategies will be essential for mitigating adverse effects on participants, stakeholders and spectators alike. From personalised interventions for athletes and attendees to comprehensive measures implemented by organisers, a holistic approach is crucial to address these challenges and the possible interplay of heat, air and water quality factors during the event. This evidence-based review highlights various environmental challenges anticipated at Paris 2024, offering strategies applicable to athletes, stakeholders and spectators. Additionally, it provides recommendations for Local Organising Committees and the International Olympic Committee that may be applicable to future Games. In summary, the review offers solutions for consideration by the stakeholders responsible for and affected by the anticipated environmental challenges at Paris 2024.
What does good care look like to people living with congenital heart disease in the 21st century? Qualitative online, asynchronous discussion forums
Authors: Wray Jo , Pagel Christina , Coats Louise , Chester Adrian H , Kennedy Fiona , Crowe Sonya
Published: July 2024

Objectives

As part of a wider study, our aim was to elicit perspectives of people with congenital heart disease (CHD) and/or their parents/carers about their experiences of healthcare and what is important to them when receiving care.

Design and setting

A qualitative study involving a series of closed, asynchronous, online discussion forums underpinned by an interpretivist framework and set up and moderated by three patient charities via their Facebook pages.

Participants

People with CHD and parents/carers of people with CHD from the UK.

Results

Five forums were run for 12–24 weeks across the three charities, and 343 participants signed up to the forums. Four linked themes related to processes of care were identified following thematic analysis of the transcripts: relationships and communication; access and coordination; experience of discrete episodes of care and psychological support. These impacted how care was experienced and, for some patients, outcomes of CHD and its treatment as well as broader health outcomes. In addition, context relating to stages of the patient journey was described, together with patient-related factors such as patients’ knowledge and expertise in their own condition.

Conclusions

People with CHD and their parents/carers want individualised, person-centred care delivered within an appropriately resourced, multidisciplinary service. Although examples of excellent care were provided it is evident that, from the perspective of patients and parents/carers, some National Health Service Standards for people with CHD were not being met.
Pancreatic STAT5 activation promotes Kras
G12D
-induced and inflammation-induced acinar-to-ductal metaplasia and pancreatic cancer
Authors: Lin Yuli , Pu Shaofeng , Wang Jun , Wan Yaqi , Wu Zhihao , Guo Yangyang , Feng Wenxue , Ying Ying , Ma Shuai , Meng Xiang Jun , Wang Wenquan , Liu Liang , Xia Qing , Yang Xuguang
Published: July 2024

Objective

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear.

Design

We performed studies with
LSL-Kras
G12D
;
Ptf1a-Cre
ERT
(KC
ERT
) mice or LSL-Kras
G12D
;

LSL-Trp53
R172H

;
Pdx1-Cre
(KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice.

Results

The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1β and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation.

Conclusion

Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.
Intergenerational transmission of health inequalities: towards a life course approach to socioeconomic inequalities in health – a review
Authors: Houweling Tanja A J , Grünberger Ilona
Published: July 2024

Adult health inequalities are a persistent public health problem. Explanations are usually sought in behaviours and environments in adulthood, despite evidence on the importance of early life conditions for life course outcomes. We review evidence from a broad range of fields to unravel to what extent, and how, socioeconomic health inequalities are intergenerationally transmitted.

We find that transmission of socioeconomic and associated health (dis)advantages from parents to offspring, and its underlying structural determinants, contributes substantially to socioeconomic inequalities in adult health. In the first two decades of life—from conception to early adulthood—parental socioeconomic position (SEP) and parental health strongly influence offspring adult SEP and health. Socioeconomic and health (dis)advantages are largely transmitted through the same broad mechanisms. Socioeconomic inequalities in the fetal environment contribute to inequalities in fetal development and birth outcomes, with lifelong socioeconomic and health consequences. Inequalities in the postnatal environment—especially the psychosocial and learning environment, physical exposures and socialisation—result in inequalities in child and adolescent health, development and behavioural habits, with health and socioeconomic consequences tracking into adulthood. Structural factors shape these mechanisms in a socioeconomically patterned and time-specific and place-specific way, leading to distinct birth-cohort patterns in health inequality.

Adult health inequalities are for an important part intergenerationally transmitted. Effective health inequality reduction requires addressing intergenerational transmission of (dis)advantage by creating societal circumstances that allow all children to develop to their full potential.
Regional inequalities in excess mortality and its community determinants during the early COVID-19 pandemic in South Korea
Authors: Kim Eunah , Lee Woojoo , Cho Sung-Il
Published: July 2024

Background

Excess mortality during the COVID-19 pandemic provides a comprehensive measure of disease burden, and its local variation highlights regional health inequalities. We investigated local excess mortality in 2020 and its determinants at the community level.

Methods

We collected data from 250 districts in South Korea, including monthly all-cause mortality for 2015–2020 and community characteristics from 2019. Excess mortality rate was defined as the difference between observed and expected mortality rates. A Seasonal Autoregressive Integrated Moving Average model was applied to predict the expected rates for each district. Penalized regression methods were used to derive relevant community predictors of excess mortality based on the elastic net.

Results

In 2020, South Korea exhibited significant variation in excess mortality rates across 250 districts, ranging from no excess deaths in 46 districts to more than 100 excess deaths per 100 000 residents in 30 districts. Economic status or the number of medical centres in the community did not correlate with excess mortality rates. The risk was higher in ageing, remote communities with limited cultural and sports infrastructure, a higher density of welfare facilities, and a higher prevalence of hypertension. Physical distancing policies and active social engagement in voluntary activities protected from excess mortality.

Conclusion

Substantial regional disparities in excess mortality existed within South Korea during the early stages of COVID-19 pandemic. Weaker segments of the community were more vulnerable. Local governments should refine their preparedness for future novel infectious disease outbreaks, considering community circumstances.
Anticipatory gaps challenge the public governance of heritable human genome editing
Authors: Rueda Jon , Segers Seppe , Hopster Jeroen , Kudlek Karolina , Liedo Belén , Marchiori Samuela , Danaher John
Published: July 2024

Considering public moral attitudes is a hallmark of the anticipatory governance of emerging biotechnologies, such as heritable human genome editing. However, such anticipatory governance often overlooks that future morality is open to change and that future generations may perform different moral assessments on the very biotechnologies we are trying to govern in the present. In this article, we identify an ‘anticipatory gap’ that has not been sufficiently addressed in the discussion on the public governance of heritable genome editing, namely, uncertainty about the moral visions of future generations about the emerging applications that we are currently attempting to govern now. This paper motivates the relevance of this anticipatory gap, identifying the challenges it generates and offering various recommendations so that moral uncertainty does not lead to governance paralysis with regard to human germline genome editing.
‘This has given me the peace of mind I needed’: ethnographic insights into Barrett’s oesophagus screening using the capsule sponge test
Authors: Davies Elspeth
Published: July 2024

In 2021 and 2022, researchers carried out an implementation trial that considered how the capsule sponge test might be used to screen for Barrett’s oesophagus using a mobile clinic in East Anglia. This paper offers insights from 15 months of ethnographic fieldwork studying the trial. It aims to highlight the value of the test in offering reassurance to worried patients, particularly to those with a family history of oesophageal adenocarcinoma. It also considers the variety of aims people held for the capsule sponge test, including the hope that it would address their symptoms of acid reflux, and the conflict that sometimes emerged as a result. The second half of the paper uses fieldwork carried out in virtual support groups for people with Barrett’s oesophagus to explore experiences postdiagnosis, which sometimes were defined by fear of future cancers. It describes notable differences between the care offered to people with morphological risk conditions like Barrett’s oesophagus and the care given to those with genetic risk conditions, including the provision of genetic counselling. More broadly, the paper highlights a tension between patient-centred and risk-centred medicine that is likely to grow as healthcare services continue to shift towards preventative approaches.
Mortality and cancer incidence in a population exposed to TCDD after the Seveso, Italy, accident (1976–2013)
Authors: Consonni Dario , Rognoni Magda , Cavalieri d'Oro Luca , Pesatori Angela Cecilia
Published: July 2024

Objectives

The Seveso accident (1976) caused the contamination with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in an area north of Milan, Italy. We report the results of the update of mortality and cancer incidence in the exposed population through 2013.

Methods

The study cohort includes subjects living in three contaminated zones with decreasing TCDD soil concentrations (zone A, B and R) and in a surrounding uncontaminated territory (reference). Poisson models stratified/adjusted for gender, age and period were fitted to calculate rate ratios (RRs) and 95% CIs.

Results

In zone A in males, we found elevated mortality from circulatory diseases in the first decade after the accident (17 deaths, RR 2.00, 95% CI 1.24 to 3.23). In females, mortality from diabetes mellitus was increased, with a positive trend across zones. Incidence of soft tissue sarcoma was increased in males in zone R in the first decade (6 cases, RR 2.62, 95% CI 1.01 to 6.83). In females in zone B, there was an excess of non-Hodgkin’s lymphoma after 30 years (6 cases, RR 2.87, 95% CI 1.14 to 7.23). Multiple myeloma was increased in the second decade in females in zone B (4 cases, RR 5.09, 95% CI 1.82 to 14.2) and in males in zone R (11 cases, RR 2.15, 95% CI 1.08 to 4.26). In males in zone R, there was a leukaemia excess after 30 years (23 cases, RR 2.02, 95% CI 1.04 to 3.93).

Conclusions

Although with different patterns across gender, zone and time, we confirmed previous results of increased cardiovascular diseases, diabetes, soft tissue sarcoma, and lymphatic and haematopoietic cancers.
Sex and race disparities in the association between work characteristics and vitamin D deficiency: findings from the National Health and Nutrition Examination Survey, 2005–2010
Authors: Velazquez-Kronen Raquel , MacDonald Leslie A , Millen Amy E
Published: July 2024

Objectives

Vitamin D deficiency is highly prevalent worldwide; however, few large population-based studies have examined occupational risk factors. We examined associations between shift work, work schedule, hours worked, outdoor work, occupation and serum 25-hydroxyvitamin D (25(OH)D) levels in the US working population.

Methods

This cross-sectional study included 8601 workers from the 2005–2010 National Health and Nutrition Examination Survey (NHANES) cycles. NHANES occupational data were supplemented with measures of outdoor work from the Occupational Information Network. Serum 25(OH)D concentration in nanomoles per litre (nmol/L) was categorised as sufficient (≥75), insufficient (50–<75), moderately deficient (30–<50) and severely deficient (<30). Age-adjusted weighted multinomial and binary logistic regression were used to examine associations between work-related factors and vitamin D status with sex-race/ethnicity stratification.

Results

Shift workers had higher odds of severe vitamin D deficiency compared with day workers (OR: 1.64, 95% CI 1.22 to 2.19). Compared with those in white-collar occupations, those in natural resources were less likely to be deficient (OR: 0.31, 95% CI 0.19 to 0.52), while those in production were more likely to be deficient (OR: 2.25, 95% CI 1.48 to 3.43). Women working ≥40 hours/week compared with <40 hours/week were more likely to be moderately deficient (OR: 1.30, 95% CI 1.06 to 1.59). Black women working in sales were more likely to be deficient than those in management (OR: 1.53, 95% CI 1.03 to 2.27). Mexican American men working nights had the highest odds of deficiency (OR: 2.64, 95% CI 1.38 to 5.06).

Conclusions

Work-related factors were associated with vitamin D status and there were race/ethnicity and sex differences. Targeted vitamin D screening and supplementation interventions may reduce these disparities.
Knowledge, attitudes and practices regarding respirable silica exposure and personal protective equipment use among brick kiln workers in Nepal
Authors: Gaviola Chelsea , Nicolaou Laura , Sharma Arun K , Chandyo Ram , Parker David , Shrestha Laxman , Das Santa K , Ramachandran Gurumurthy , Thygerson Steven M , Beres Laura , Checkley William
Published: July 2024

Objectives

Brick kiln workers in Nepal are a neglected population who are exposed to high respirable silica concentrations, and few use interventions to reduce exposure. We aimed to characterise the prevalence of respiratory personal protective equipment (PPE) use, understand knowledge and attitudes towards kiln dust and respiratory PPE and identify factors associated with respiratory PPE use.

Methods

We conducted a cross-sectional study in Bhaktapur, Nepal. We used simple random selection to identify 10 out of 64 total kilns and stratified random sampling of 30 households to enrol workers aged ≥14 years within selected kilns. Field workers surveyed participants using structured questionnaires. Our primary outcome was to characterise the prevalence of current respiratory PPE use and secondary outcomes were summaries of knowledge, attitudes and practice of PPE use.

Results

We surveyed 83 workers (mean age 30.8 years, 77.1% male). Of these, 28.9% reported current respiratory PPE use at work, 3.6% heard of silicosis prior to the survey and 24.1% correctly identified the best respiratory PPE (N95, compared with surgical masks and barrier face coverings) for reducing dust exposure. Respiratory PPE users had higher income (mean monthly household income US$206 vs US$145; p=0.04) and education levels (25% vs 5.1% completed more than primary school; p=0.02) compared with non-users.

Conclusions

Respiratory PPE use was low. Workers had poor knowledge of kiln dust health effects and proper respiratory PPE. We highlight important barriers to PPE use, particularly knowledge gaps, which can guide future investigations to reduce the silicosis burden among brick kiln workers.
Mechanisms of end-of-life communication contributing to optimal care at the end of life: a review of reviews
Authors: Khonsari Sahar , Johnston Bridget , Patterson Hannah , Mayland Catriona
Published: July 2024

Background

End-of-life communication is an essential component of high-quality care, but its potential mechanisms for improving care are not well understood.

Objectives

To summarise the potential mechanisms by which end-of-life communication may contribute to enhanced end-of-life care in any setting.

Design

An overview of systematic reviews, with a narrative synthesis of results. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Study quality was assessed using the AMSTAR (A MeaSurement Tool to Assess Reviews) tool.

Data sources

CINAHL, MEDLINE, Cochrane, SSCI and PsycINFO databases, were searched from inception to January 2024. Manual searches were also conducted.

Eligibility criteria for selecting studies

Systematic reviews (published in English) related to end-of-life communication, where the target population was adult patients in their last year of life, relatives, caregivers and/or healthcare professionals involved in communicating with dying patients.

Results

We reviewed 35 eligible studies. The reviews suggest potential mechanisms of effective end-of-life communication including collaborative decision-making, tailoring communication to individuals, using effective communication strategies and incorporating communication skills into practice. The reviews also highlighted barriers related to patients, professionals and organisations.

Conclusion

This review highlights a nuanced understanding of potential mechanisms of end-of-life communication, emphasising the need for tailored training, policy enhancements and interprofessional collaboration. It calls on healthcare professionals to reflect on their practices, advocating for co-designing a person-centred communication model that addresses patient preferences at the end of life. Importantly, in culturally diverse contexts, there is a need for a communication paradigm that embraces diversity to provide truly empathetic and effective end-of-life care. This concise roadmap may foster compassionate, dignified and effective end-of-life communication.

Trial registration number

Protocol registered with PROSPERO (CRD42022271433, 29 March 2022).
Hospice inpatient care models: cross-sectional inequality survey
Authors: Tween Suzanne , Smith Roger William , Chamberlain Charlotte , Gibbins Jane
Published: July 2024

Objectives

Hospices provide a range of services including inpatient units (IPUs) and care in people’s homes. 40 000–50 000 patients use IPUs in the UK per year. Little published data exist on IPU models. This paper explores the structure and funding of IPU across the Southwest (SW) of England (population 5.6 million), alongside impact of COVID-19.

Methods

An electronic survey of all 13 IPUs. Data collated, tabulated and compared with national commissioning guidance.

Results

A 92% survey response rate revealed large variation in bed availability per 250 000 of SW population: 2.5–18.2. Referrals and admissions per IPU bed per year ranged from 16 to 38.2 (or 39–127 per 100 000 population) and 21.7 (mean), respectively. There was significant workforce variability: 1.3–12.7 nurses per 7.5 hospice beds, 1.2–7.2 consultants per 20 hospice beds, varying multidisciplinary team members with many unfilled posts. National Health Service (NHS) funding ranged from 10% to 75% of total costs. During COVID-19, 4 of 12 hospices reduced bed capacity, while half described increased integration with other teams outside of the hospice.

Conclusion

There is significant regional variability suggesting inequality in hospice bed availability per 250 000 population. There is also considerable variability in workforce, alongside the proportion of NHS funding. Such variability implies little is known about the optimal IPU model. This provides new meaningful information about the structure and funding of hospices, with further research needed to consider these differences on the impact on patient and family experiences and outcomes. The sustainability and opportunities of integration and collaboration across care settings are also paramount.
Pseudo-random number generation based on spatial chaotic map of Logistic type and its cryptographic application
Authors: Sun Fuyan , Lv Zongwang , Wang Caihong
Published: July 2024

The pseudo-random number generator (PRNG) based on chaos has been widely used in the fields of digital communication, cryptography and computer simulation. In this paper, we study a new PRNG based on spatial surface chaotic system (SSCS), which is constructed based on coupling mapping lattice (CML) and one-dimensional Logistic chaotic map. To verify the performance of this generator, we study its nonlinear dynamic properties, including the Lyapunov exponent, ergodicity and bifurcation phenomena. Moreover, we analyze the cryptographic properties such as key space, key sensitivity, correlation, histogram and information entropy, while performing NIST SP800-22 test and TestU01 test for the randomness of this system. Theoretical analysis and numerical simulation results show that the PRNG proposed in this paper has good complexity, ergodicity, sensitivity and randomness. Moreover, the key space can increase dynamically with the increase of encrypted data, especially suitable for the protection of big data such as multimedia, which is more advantageous than most existing chaotic mapping. The results of this paper will provide a new idea for the study of chaotic cryptography, and motivate the study of new discrete chaotic models with desirable statistical properties.
Understanding and Generalizing Unique Decompositions of Generators of Dynamical Semigroups
Authors: vom Ende Frederik
Published: July 2024

We generalize the result of Gorini, Kossakowski, and Sudarshan [J. Math. Phys. 17:821, 1976] that every generator of a quantum-dynamical semigroup decomposes uniquely into a closed and a dissipative part, assuming the trace of both vanishes. More precisely, we show that given any generator [Formula: see text] of a completely positive dynamical semigroup and any matrix [Formula: see text] there exists a unique matrix [Formula: see text] and a unique completely positive map [Formula: see text] such that (i) [Formula: see text], (ii) the superoperator [Formula: see text] has trace zero, and (iii) [Formula: see text] is a real number. The key to proving this is the relation between the trace of a completely positive map, the trace of its Kraus operators, and expectation values of its Choi matrix. Moreover, we show that the above decomposition is orthogonal with respect to some [Formula: see text]-weighted inner product.
SQL2FPGA: Automated Acceleration of SQL Query Processing on Modern CPU-FPGA Platforms
Authors: Lu Alec , Narendra Agrawal Jahanvi , Fang Zhenman
Published: July 2024

Today’s big data query engines are constantly under pressure to keep up with the rapidly increasing demand for faster processing of more complex workloads. In the past few years, FPGA-based database acceleration efforts have demonstrated promising performance improvement with good energy efficiency. However, few studies target the programming and design automation support to leverage the FPGA accelerator benefits in query processing. Most of them rely on the SQL query plan generated by CPU query engines and manually map the query plan onto the FPGA accelerators, which is tedious and error-prone. Moreover, such CPU-oriented query plans do not consider the utilization of FPGA accelerators and could lose more optimization opportunities.

In this article, we present SQL2FPGA, an FPGA accelerator-aware compiler to automatically map SQL queries onto the heterogeneous CPU-FPGA platforms. Our SQL2FPGA front-end takes an optimized logical plan of an SQL query from a database query engine and transforms it into a unified operator-level intermediate representation. To generate an optimized FPGA-aware physical plan, SQL2FPGA implements a set of compiler optimization passes to (1) improve operator acceleration coverage by the FPGA, (2) eliminate redundant computation during physical execution, and (3) minimize data transfer overhead between operators on the CPU and FPGA. Furthermore, it also leverages machine learning techniques to predict and identify the optimal platform, either CPU or FPGA, for the physical execution of individual query operations. Finally, SQL2FPGA generates the associated query acceleration code for heterogeneous CPU-FPGA system deployment. Compared to the widely used Apache Spark SQL framework running on the CPU, SQL2FPGA—using two AMD/Xilinx HBM-based Alveo U280 FPGA boards and Ver.2020 AMD/Xilinx FPGA overlay designs—achieves an average performance speedup of 10.1x and 13.9x across all 22 TPC-H benchmark queries in a scale factor of 1 GB (SF1) and 30 GB (SF30), respectively. While evaluated on AMD/Xilinx Alveo U50 FPGA boards, SQL2FPGA using Ver. 2022 AMD/Xilinx FPGA overlay designs also achieve an average speedup of 9.6x at SF1 scale factor.