bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in prevalence and sociodemographic correlates of tobacco and nicotine use in Finland during the COVID-19 pandemic
Authors: Peña Sebastián , Ilmarinen Katja , Kestilä Laura , Ruokolainen Otto , Ollila Hanna , Parikka Suvi , Karvonen Sakari
Published: July 2023

Background

The impact of the coronavirus disease 2019 (COVID-19) pandemic on tobacco and nicotine use remains debated. We examined whether the prevalence of tobacco and nicotine use and nicotine-replacement therapy (NRT) changed during the COVID-19 pandemic and whether changes differed by sociodemographic groups.

Methods

Repeated cross-sectional study of three national surveys in Finland (2018, 2019 and 2020; n = 58 526 adults aged 20 and over). Outcomes were daily and occasional smoking, smokeless tobacco (snus) use, e-cigarettes use, total tobacco or nicotine use and NRT use. We examined changes for each outcome by sex, age, educational tertiles, marital status, mother tongue and social participation.

Results

Daily smoking decreased among males by 1.15 percentage points (pp) [95% confidence interval (CI) −2.10 to −0.20] between 2018 and 2020 and 0.86 pp among females (95% CI −1.58 to −0.15). Daily snus use remained stable in both sexes. Daily e-cigarette use was below 1% and remained stable. We found weak evidence of a reduction in total tobacco or nicotine use between 2018 and 2020 (males −1.18 pp, 95% CI −2.68 to 0.32 and females −0.8 pp, 95% CI −1.81 to 0.22). NRT use remained stable. Snus and NRT use decreased among 60- to 74-year-olds but remained stable in other age groups. We did not find evidence of interactions by subgroup for other outcomes.

Conclusions

Daily smoking decreased in Finland between 2018 and 2020, but other forms of tobacco use did not experience a reduction. The COVID-19 pandemic does not seem to have altered the sustained reduction of smoking in Finland, although substantial sociodemographic differences persist.
Improved accuracy of plane-wave electromagnetic modelling by application of the total and scattered field decomposition and perfectly matched layers
Authors: Buntin L M , Kalscheuer T , Kreiss G , Ren Z
Published: July 2023

In 2-D magnetotelluric modelling, the standard application of Dirichlet boundary conditions (BC) may severely diminish the solution accuracy, because the unknown scattered part of the electromagnetic field is erroneously reflected at the domain boundary. Therefore, we adapt the total and scattered field decomposition (TSFD) to geophysical modelling, enabling the application of fully absorbing boundary methods, here perfectly matched layers (PML), to the scattered field. Our novel TSFD divides the modelling domain into two regions. In the total-field region containing the area of interest, the solution is computed for the total field. In the scattered-field region containing the boundaries, the solution is obtained for the scattered field, which is fully absorbed by PML at the boundaries. The plane-wave source is excited at the TSFD interface between both regions. Thus, boundary reflections are eradicated leading to superior solution accuracy, and boundaries can be placed closer to the receivers, shrinking the computational problem. Especially for challenging models with strong lateral changes, the solution accuracy of the TSFD is superior to that of the standard Dirichlet approach. Owing to the linearity of Maxwell’s equations, the inaccuracy introduced to the electric and magnetic fields by using Dirichlet BC can be expected to partly cancel out in the magnetotelluric transfer functions, for example the impedance tensor. In this work, we quantify this cancellation effect. The inaccuracy is less than typical measurement errors in the vast majority of apparent resistivity and phase data, even, when the primary fields are strongly inaccurate.
Isolation and application of pH- and salt-resistant Bacillus strains to reduce ammonia emission from pig manure during the storage period
Authors: Shen Weishou , Dai Haiyang , Gu Shenyi , Guo Fanjing , Li Tianling , Rajasekar Adharsh
Published: July 2023

Aim

Ammonia released during the storage period from pig manure causes severe air pollution and odor issues, ultimately leading to nitrogen loss in the manure. In this study, we investigated the application of 13 Bacillus spp. strains isolated from paddy soil and their potential to minimize reactive nitrogen loss during pig manure storage at 28°C and initial moisture content at 76.45%.

Methods and results

We selected five strains of Bacillus spp. named H3-1, H4-10, H5-5, H5-9, and Y3-28, capable of reducing ammonia emissions by 23.58%, 24.65%, 25.58%, 25.36%, and 26.82% in pig manure over 60 days compared to control. We further tested their ability on various pH, salinity, and ammonium-nitrogen concentrations for future field applications. Our investigation revealed that certain bacteria could survive and grow at pH 6, 8, and 10; 4, 8, and 10% salinity and up to 8 g l−1 of ammonium-nitrogen concentration.

Conclusions

The results from our study show that saline and ammonium–nitrogen tolerant Bacillus strains isolated from soil can potentially reduce ammonia emissions in pig manure, even at high moisture content during their storage period.
Lipopolysaccharide promotes apoptosis and oxidative injury of porcine small intestinal epithelial cells by down-regulating the expression of glutamine transporter ASCT2
Authors: Tang Xiaopeng , Xiong Kangning , Liu Jia , Li Meijun
Published: July 2023

The present study aimed to investigate the effects of lipopolysaccharide (LPS) stimulation on oxidative damage, apoptosis, and glutamine (Gln) transporter Alanine-Serine-Cysteine transporter 2 (ASCT2) expression in porcine small intestinal epithelial cells (IPEC-J2), and preliminarily elucidated the relationship between ASCT2 expression level and oxidative damage and apoptosis of IPEC-J2 cells. IPEC-J2 cells were treated without (control group, CON, N = 6) or with 1 μg/mL LPS (LPS group, LPS, N = 6). Cell viability, lactate dehydrogenase (LDH) content, malonaldehyde (MDA), anti-oxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px], and total anti-oxidant capacity [T-AOC]), apoptosis of IPEC-J2 cells, the expression of Caspase3, the expression of ASCT2 mRNA and ASCT2 protein was detected. The results showed that LPS stimulation of IPEC-J2 cells significantly reduced the cell viability, and anti-oxidant enzymes activity (SOD, CAT, and GSH-Px), and significantly increased LDH and MDA release. Flow cytometry results showed that LPS stimulation significantly increased the late apoptosis rate and the total apoptosis rate of IPEC-J2 cells. The immunofluorescence results showed that the fluorescence intensity of LPS stimulated IPEC-J2 cells was significantly enhanced. LPS stimulation significantly decreased the mRNA and protein expression of ASCT2 in IPEC-J2 cells. The correlation analysis showed that ASCT2 expression was negatively correlated with apoptosis, and positively correlated with the anti-oxidant capacity of IPEC-J2 cells. According to the results of this study, it can be preliminarily concluded that LPS promotes the apoptosis and oxidative injury of IPEC-J2 cells by down-regulating the expression of ASCT2.
Hydrogen bonds connecting the N-terminal region and the DE loop stabilize the monomeric structure of transthyretin
Authors: Inada Yuki , Ono Yuichiro , Okazaki Kyo , Yamashita Takuma , Kawaguchi Tomoyuki , Kawano Shingo , Kobashigawa Yoshihiro , Shinya Shoko , Kojima Chojiro , Shuto Tsuyoshi , Kai Hirofumi , Morioka Hiroshi , Sato Takashi
Published: July 2023

Transthyretin (TTR) is a homo-tetrameric serum protein associated with sporadic and hereditary systemic amyloidosis. TTR amyloid formation proceeds by the dissociation of the TTR tetramer and the subsequent partial unfolding of the TTR monomer into an aggregation-prone conformation. Although TTR kinetic stabilizers suppress tetramer dissociation, a strategy for stabilizing monomers has not yet been developed. Here, we show that an N-terminal C10S mutation increases the thermodynamic stability of the TTR monomer by forming new hydrogen bond networks through the side chain hydroxyl group of Ser10. Nuclear magnetic resonance spectrometry and molecular dynamics simulation revealed that the Ser10 hydroxyl group forms hydrogen bonds with the main chain amide group of either Gly57 or Thr59 on the DE loop. These hydrogen bonds prevent the dissociation of edge strands in the DAGH and CBEF β-sheets during the unfolding of the TTR monomer by stabilizing the interaction between β-strands A and D and the quasi-helical structure in the DE loop. We propose that introducing hydrogen bonds to connect the N-terminal region to the DE loop reduces the amyloidogenic potential of TTR by stabilizing the monomer.
Transcriptional pausing induced by ionizing radiation enables the acquisition of radioresistance in nasopharyngeal carcinoma
Authors: Liu Honglu , Fu Huanyi , Yu Chunhong , Zhang Na , Huang Canhua , Lv Lu , Hu Chunhong , Chen Fang , Xiao Zhiqiang , Zhang Zhuohua , Lu Huasong , Yuan Kai
Published: July 2023

Lesions on the DNA template can impact transcription via distinct regulatory pathways. Ionizing radiation (IR) as the mainstay modality for many malignancies elicits most of the cytotoxicity by inducing a variety of DNA damages in the genome. How the IR treatment alters the transcription cycle and whether it contributes to the development of radioresistance remain poorly understood. Here, we report an increase in the paused RNA polymerase II (RNAPII), as indicated by the phosphorylation at serine 5 residue of its C-terminal domain, in recurrent nasopharyngeal carcinoma (NPC) patient samples after IR treatment and cultured NPC cells developing IR resistance. Reducing the pool of paused RNAPII by either inhibiting TFIIH-associated CDK7 or stimulating the positive transcription elongation factor b, a CDK9–CycT1 heterodimer, attenuates IR resistance of NPC cells. Interestingly, the poly(ADP-ribosyl)ation of CycT1, which disrupts its phase separation, is elevated in the IR-resistant cells. Mutation of the major poly(ADP-ribosyl)ation sites of CycT1 decreases RNAPII pausing and restores IR sensitivity. Genome-wide chromatin immunoprecipitation followed by sequencing analyses reveal that several genes involved in radiation response and cell cycle control are subject to the regulation imposed by the paused RNAPII. Particularly, we identify the NIMA-related kinase NEK7 under such regulation as a new radioresistance factor, whose downregulation results in the increased chromosome instability, enabling the development of IR resistance. Overall, our results highlight a novel link between the alteration in the transcription cycle and the acquisition of IR resistance, opening up new opportunities to increase the efficacy of radiotherapy and thwart radioresistance in NPC.
Constructions of Multiple Deservingness Frames towards Refugees in Everyday Work Life in İzmir
Authors: Siviş Selin , Yıldız Ayselin
Published: July 2023

This study focuses on the role of justification astrategies in the production and mobilization of multiple deservingness framings towards refugees in everyday work life. Drawing on in-depth interviews with Turkish employers in labour-intensive sectors in İzmir, the article presents a city-centred, evidence supported case which answers on the basis of which criteria Syrian refugee workers are deemed deserving and undeserving. It argues that the production of deservingness frames is not uniform and mutable across time and space, thereby actors can engage in different justification strategies in similar situations since the constitution and mobilization of deservingness frames are context-dependent. This study further argues that Turkish employers’ narratives towards Syrian refugee workers are shaped by not only economic interests but also unique features of historical and socio-cultural dynamics at the local level, resulting in three distinct deservingness frames: established deservingness, fragile deservingness, and established undeservingness.
The extremely X-ray luminous radio-loud quasar CFHQS J142952 + 544717 at z = 6.18 under Chandra high-angular resolution lens
Authors: Migliori G , Siemiginowska A , Sobolewska M , Cheung C C , Stawarz Ł , Schwartz D , Snios B , Saxena A , Kashyap V
Published: July 2023

We present the first X-ray observation at sub-arcsecond resolution of the high-redshift (z = 6.18) radio-loud quasar CFHQS J142952 + 544717 (J1429). The ∼100 net-count 0.3–7 keV spectrum obtained from ∼30 ks Chandra exposure is best fit by a single power-law model with a photon index Γ = 2.0 ± 0.2 and no indication of an intrinsic absorber, implying a 3.6–72 keV rest-frame luminosity $L_{\rm X}=(2.3^{+0.6}_{-0.5})\times 10^{46}$ erg s−1. We identify a second X-ray source at 30″ distance from J1429 position, with a soft (Γ ≃ 2.8) and absorbed (equivalent hydrogen column density NH < 13.4 × 1020 cm−2) spectrum, which likely contaminated J1429 spectra obtained in lower angular resolution observations. Based on the analysis of the Chandra image, the bulk of the X-ray luminosity is produced within the central ∼3 kpc region, either by the disc/corona system, or by a moderately aligned jet. In this context, we discuss the source properties in comparison with samples of low- and high-redshift quasars. We find indication of a possible excess of counts over the expectations for a point-like source in a 0.5″–1.5″ (∼3−8 kpc) annular region. The corresponding X-ray luminosity at J1429 redshift is 4 × 1045 erg s−1. If confirmed, this emission could be related to either a large-scale X-ray jet, or a separate X-ray source.
Modelling planet-induced gaps and rings in ALMA discs: the role of in-plane radiative diffusion
Authors: Ziampras Alexandros , Nelson Richard P , Rafikov Roman R
Published: July 2023

ALMA observations of protoplanetary discs in dust continuum emission reveal a variety of annular structures. Attributing the existence of such features to embedded planets is a popular scenario, supported by studies using hydrodynamical models. Recent work has shown that radiative cooling greatly influences the capability of planet-driven spiral density waves to transport angular momentum, ultimately deciding the number, position, and depth of rings and gaps that a planet can carve in a disc. However, radiation transport has only been treated via local thermal relaxation, not taking into account radiative diffusion along the disc plane. We compare the previous state-of-the-art models of planet–disc interaction with local cooling prescriptions to our new models that include cooling in the vertical direction and radiative diffusion in the plane of the disc, and show that the response of the disc to the induced spiral waves can differ significantly when comparing these two treatments of the disc thermodynamics. We follow up with synthetic emission maps of ALMA systems, and show that our new models reproduce the observations found in the literature better than models with local cooling. We conclude that appropriate treatment of radiation transport is key to constraining the parameter space when interpreting ALMA observations using the planet–disc interaction scenario.
A rare outburst from the stealthy BeXRB system Swift J0549.7−6812
Authors: Coe M J , Kennea J A , Monageng I M , Buckley D A H , Udalski A , Evans P A
Published: July 2023

Swift J0549.7−6812 is a Be/X-ray binary system (BeXRB) in the Large Magellanic Cloud (LMC) exhibiting an ∼6 s pulse period. Like many such systems, the variable X-ray emission is believed to be driven by the underlying behaviour of the mass donor Be star. In this paper, we report on X-ray observations of the brightest known outburst from this system, which reached a luminosity of ∼8 × 1037 erg s−1. These observations are supported by contemporaneous optical photometric observations, the first reported optical spectrum, as well as several years of historical data from Optical Gravitational Lens Explorer (OGLE) and Gaia. The latter strongly suggest a binary period of 46.1 d. All the observational data indicate that Swift J0549.7−6812 is a system that spends the vast majority of its time in X-ray quiescence, or even switched off completely. This suggests that occasional observations may easily miss it, and many similar systems, and thereby underestimate the massive star evolution numbers for the LMC.
Evaluation of the Rheumatoid Arthritis Observation of Biologic Therapy risk score in Japanese patients with rheumatoid arthritis starting first biologic disease–modifying antirheumatic drugs: A validation study using the Institute of Rheumatology, Rheumatoid Arthritis cohort data
Authors: Higuchi Tomoaki , Tanaka Eiichi , Inoue Eisuke , Abe Mai , Saka Kumiko , Sugano Eri , Sugitani Naohiro , Higuchi Yoko , Ochiai Moeko , Yamaguchi Rei , Ikari Katsunori , Yamanaka Hisashi , Harigai Masayoshi
Published: July 2023

Objectives

This article aims to examine the ability of the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk score to predict the occurrence of serious infections in Japanese patients with rheumatoid arthritis (RA), after initiating their first biologic disease–modifying antirheumatic drug (bDMARD).

Methods

We used data from the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2008 to 2020. Patients with RA who were started on their first bDMARDs were included. Those with missing data required to calculate the score were excluded. A receiver operating characteristic curve was used to evaluate the discriminatory ability of the RABBIT score.

Results

A total of 1081 patients were enrolled. During the 1-year observational period, 23 (1.7%) patients had serious infections; the most frequent one was bacterial pneumonia (n = 11, 44%). The median RABBIT score in the serious infection group was significantly higher than that in the non-serious infection group [2.3 (1.5–5.4) vs 1.6 (1.2–2.5), P < .001]. The area under the receiver operating characteristic curve for the occurrence of serious infections was 0.67 (95% confidence interval 0.52–0.79), suggesting that the score had low accuracy.

Conclusions

Our present study revealed that the RABBIT risk score did not have sufficient discriminatory ability for predicting the development of severe infections in Japanese patients with RA after initiating their first bDMARD.
A novel long noncoding RNA—lncRNA‐AABR07066529.3 alleviates inflammation, apoptosis, and pyroptosis by inhibiting MyD88 in lipopolysaccharide‐induced myocardial depression
Authors: Wen Ri , Zhang Tie‐Ning , Zhang Tao , Tong Yu‐Jing , Song Wen‐Liang , Liu Yong‐Ping , Yang Ni , Liu Chun‐Feng
Published: July 2023

Sepsis‐induced myocardial depression (SIMD) is common in pediatric intensive care units and seriously threatens children's health. Recently, long noncoding RNAs (lncRNAs) have been showed to play important roles in various diseases; however, its role in SIMD is unclear. In this study, we used lipopolysaccharide (LPS)‐treated rats and H9c2 cardiomyocytes to mimic SIMD in vivo and in vitro. We found that the expression of a novel lncRNA, we named lncRNA‐AABR07066529.3, was elevated in LPS‐induced rat heart tissue and H9c2 cardiomyocytes. In addition, LPS‐induced inflammation, apoptosis, and pyroptosis were significantly exacerbated after lncRNA‐AABR07066529.3 knockdown. Moreover, we found that myeloid differentiation factor 88 (MyD88) was upregulated in LPS‐treated groups and was inhibited by lncRNA‐AABR07066529.3. Besides, MyD88 knockdown abolished lncRNA‐AABR07066529.3 silencing effects on inflammation, apoptosis, and pyroptosis induced by LPS in H9c2 cardiomyocytes. In our study, we found lncRNA‐AABR07066529.3 exerted protective effects on LPS‐induced cardiomyocytes by regulating MyD88 and might serve as a potential treatment target for SIMD.
Examining the Use of a Polypill in Cardiovascular Disease Prevention
Authors: Wang Andy , Veasaw Kassidy , Subhan Sarah , Patel Jay , Frishman William H.
Published: July 2023

Cardiovascular disease (CVD) is a significant cause of death worldwide. To address the global burden of CVD and its risk factors, the polypill, an all-in-one therapy that combines multiple existing medications for preventing CVD and reducing CVD events (such as angiotensin-converting enzyme inhibitor, beta-blocker, statin, or aspirin) into a single combination pill, has emerged as a potential strategy to improve CVD prevention. Clinical trials on the polypill have found that polypill use is associated with significant reductions in CVD events and risk factors in both patients with established CVD and at risk of developing CVD, suggesting a potential benefit in primary and secondary CVD prevention. The polypill has also been demonstrated to be a cost-effective therapy that may potentially increase treatment accessibility, affordability, and availability particularly in low- and middle-income countries. Further, patients on polypill therapy have shown high rates of treatment compliance, with significant improvements in medication adherence for patients with low baseline compliance. Given its potential advantages and benefits, the polypill may become a promising therapy for the prevention of CVD.
Agmatine prevents the memory impairment and the dysfunction of hippocampal GSK-3β and ERK signaling induced by aluminum nanoparticle in mice
Authors: Izadi Sadegh , Rezaei Amin , Esmaili Zahra , Soukhaklari Roksana , Moosavi Maryam
Published: July 2023

The growing usage of aluminum nanoparticles (Al-NP) and their exposure may influence body function. Considering the proposed relationship between Al and the pathogenesis of Alzheimer’s disease and the concern about the effect of this nanoparticle on brain health and cognitive function, the use of neuroprotective agents might be helpful. According to the reported neuroprotective effects of agmatine, in the present study, the possible protective effect of agmatine was assessed in mice model of Al-NP-induced memory impairment. In addition, due to the roles of hippocampal Glycogen synthase kinase-3 beta (GSK-3β) and ERK signaling in memory and its disorders, these pathways were also investigated. Al-NP (10 mg/kg/p.o.) with/without agmatine (5 or 10 mg/kg/i.p.) was administered to adult male NMRI mice for 5 days. Novel object recognition (NOR) test session was used to assess cognitive function. Following the behavioral assessments, the hippocampi were used to determine the phosphorylated and total levels of GSK-3β and ERK as well as GAPDH using western blot analysis. The results showed that Al-NP impaired NOR memory in mice while agmatine 10 mg/kg prevented the memory deficit induced by Al-NP. Furthermore, Al-NP activated GSK-3β as well as ERK signals within the hippocampus while agmatine prevented the effects of Al-NP on GSK-3β and ERK signals within the hippocampus. Besides supporting the neuroprotective effects of agmatine, these findings suggest the possibility of the connection of hippocampal GSK-3β and ERK signaling in the neuroprotective effect of this polyamine against Al-NP.
Serum cholesterol levels and the risk of brain natriuretic peptide–diagnosed heart failure in postmenopausal women: a population-based prospective cohort study
Authors: Arafa Ahmed , Kashima Rena , Kokubo Yoshihiro , Teramoto Masayuki , Sakai Yukie , Nosaka Saya , Kawachi Haruna , Shimamoto Keiko , Matsumoto Chisa , Nakao Yoko M. , Gao Qi , Izumi Chisato
Published: July 2023

Objective

Hormonal changes during menopause can disturb serum cholesterol which is closely associated with cardiovascular disease. This study investigated the prospective association between serum cholesterol and heart failure (HF) risk in postmenopausal women.

Methods

We analyzed data from 1,307 Japanese women, aged 55 to 94 years. All women had no history of HF, and their baseline brain natriuretic peptide (BNP) levels were less than 100 pg/mL. During the follow-ups conducted every 2 years, HF was diagnosed among women who developed BNP of 100 pg/mL or greater. Cox proportional hazard models were applied to calculate hazard ratios and 95% CI of HF for women per their baseline total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels. The Cox regression models were adjusted for age, body mass index, smoking, alcohol drinking, hypertension, diabetes, cardiac murmurs, arrhythmia, stroke or ischemic heart disease, chronic kidney disease, and lipid-lowering agent use.

Results

Within an 8-year median follow-up, 153 participants developed HF. In the multivariable-adjusted model, women with total cholesterol of 240 mg/dL or greater (compared with 160-199 mg/dL) and HDL-C of 100 mg/dL or greater (compared with 50-59 mg/dL) showed an increased risk of HF: hazard ratios (95% CI) = 1.70 (1.04-2.77) and 2.70 (1.10-6.64), respectively. The results remained significant after further adjusting for baseline BNP. No associations were observed with low-density lipoprotein cholesterol.

Conclusions

Total cholesterol of 240 mg/dL or greater and HDL-C of 100 mg/dL or greater were positively associated with the risk of HF in postmenopausal Japanese women.
Better Work Ability Is Associated With Lower Levels of Both Occupational Stress and Occupational Physical Activity in Professional Drivers
Authors: Casagrande Cynthia Mara Zilli , Farias Jean Paulo , Meziat-Filho Ney , Nogueira Leandro Alberto Calazans , Ferreira Arthur Sá
Published: July 2023

Objective

The aim of the study is to investigate the association of sociodemographic factors, lifestyle, work organization, and professional profile with work ability in professional drivers.

Methods

This is a cross-sectional study with 449 drivers in Curitiba, Paraná (Brazil). Participants were assessed regarding their work ability (Work Ability Index [WAI]), sociodemographic, lifestyle (physical activity [Baecke’s questionnaire] and stress [Work Stress Scale]), work organization, and professional profile using self-completion instruments. The association of WAI with sociodemographic factors, lifestyle, work organization, and professional profile was determined by multivariable ordinal logistic regression models.

Results

Lifestyle factors best explained the WAI variability. The WAI was inversely associated with stress and occupational physical activities but directly associated with leisure activities and locomotion and leisure-time physical exercise.

Conclusions

Our data also challenge the concept that sociodemographic information and ergonomics organization influence determining the work ability of this population.
Autologous blood transfusion reduces the requirement for peri-operative allogenic blood transfusion in patients undergoing major hepatopancreatobiliary surgery: a retrospective cohort study
Authors: Lakha Adil S , Chadha Radhika , Von-Kier Stephen , Barbosa Antonio , Maher Keith , Pirkl Martin , Stoneham Mark , Silva Michael A , Soonawalla Zahir , Udupa Venkatesha , Reddy Srikanth , Gordon-Weeks Alex
Published: July 2023

Introduction:

Major hepatopancreatobiliary surgery is associated with a risk of major blood loss. We aimed to assess whether autologous transfusion of blood salvaged intra-operatively reduces the requirement for post-operative allogenic transfusion in this patient cohort.

Materials and methods:

In this single centre study, information from a prospective database of 501 patients undergoing major HPB resection (2015–2022) was analysed. Patients who received cell salvage (n=264) were compared with those who did not (n=237). Non-autologous (allogenic) transfusion was assessed from the time of surgery to 5 days post-surgery, and blood loss tolerance was calculated using the Lemmens-Bernstein-Brodosky formula. Multivariate analysis was used to identify factors associated with allogenic blood transfusion avoidance.

Results:

32% of lost blood volume was replaced through autologous transfusion in patients receiving cell salvage. Although the cell salvage group experienced significantly higher intra-operative blood loss compared with the non-cell salvage group (1360 ml vs 971 ml, P=0.0005), they received significantly less allogenic red blood cell units (1.5 vs. 0.92 units/patient, P=0.03). Correction of blood loss tolerance in patients who underwent cell salvage was independently associated with avoidance of allogenic transfusion (OR 0.05 (0.006–0.38) P=0.005). In a subgroup analysis, cell salvage use was associated with a significant reduction in 30-day mortality in patients undergoing major hepatectomy (6% vs. 1%, P=0.04).

Conclusion:

Cell salvage use was associated with a reduction in allogenic blood transfusion and a reduction in 30-day mortality in patients undergoing major hepatectomy. Prospective trials are warranted to understand whether the use of cell salvage should be routinely utilised for major hepatectomy.
Advanced Magnetic Resonance Imaging Sheds Light on the Distinct Pathophysiology of Various Types of Acute Sensorineural Hearing Loss
Authors: Kurata Natsuko , Kawashima Yoshiyuki , Ito Taku , Fujikawa Taro , Nishio Ayako , Honda Keiji , Kanai Yasuhisa , Terasaki Mariko , Endo Ikuyo , Tsutsumi Takeshi
Published: July 2023

Objective

To compare the findings of magnetic resonance imaging (MRI) with advanced protocols in patients with various types of acute sensorineural hearing loss (ASNHL).

Study Design

Retrospective case review.

Setting

Tertiary referral center.

Patients

Two hundred eighty-seven patients with ASNHL

Interventions

All patients underwent MRI scanning, including heavily T2-weighted three-dimensional fluid-attenuated inversion recovery before and 4 hours after the intravenous administration of gadolinium contrast medium (delayed 3D-FLAIR). A hybrid of the reversed image of the positive endolymph signal and the native image of the perilymph signal image was constructed to visualize the endolymphatic space.

Results

The detection rates of abnormal MRI findings vary significantly among different types of ASNHL. A hyperintense signal on delayed 3D-FLAIR was observed in all patients with intralabyrinthine schwannoma or vestibular schwannoma and 20.5% of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) but was rarely observed in definite Ménière's disease (MD, 2.6%). In contrast, endolymphatic hydrops (EH) was frequently observed in patients with definite MD (79.5%) but was observed much less frequently in patients with ISSNHL (11.0%). In patients with cochlear MD and ALHL, detection rates of cochlear EH were similar to those with definite MD, whereas detection rates of vestibular EH were significantly lower than in patients with definite MD.

Conclusions

The significantly different detection rates of abnormal MRI findings among various types of ASNHL shed light on the distinct pathophysiology of each disorder. A diagnosis based on MRI findings with advanced protocols may help select treatment strategies and provide prognostic information for patients.
Endolymphatic Hydrops on Magnetic Resonance Imaging May Be an Independent Finding on Aging in Neurotologic Patients
Authors: Maeda Yukihide , Kojima Katsuhide , Takao Soshi , Omichi Ryotaro , Kariya Shin , Ando Mizuo
Published: July 2023

Objective

To clarify whether age impacts the development of endolymphatic hydrops (ELH) in neurotologic patients. Documentation of ELH in living patients on magnetic resonance imaging (MRI) allows analysis of patient age and formation of ELH, which is impossible by means of postmortem temporal bone pathology.

Study Design

Retrospective case review.

Setting

Tertiary referral center.

Patients

Fifty patients (100 ears) with top 3 diagnoses of definite Menière's disease, delayed ELH, or probable Menière's disease.

Interventions

Endolymph MRI after intravenous gadolinium injection and pure-tone audiometry.

Main Outcome Measures

Cochlear and vestibular ELH confirmed by MRI.

Results

The prevalences of ears showing both cochlear and vestibular ELH were similar among age groups <30 years (30%), 30–59 years (25.9%), and ≥60 years (34.4%; p > 0.05; χ
2 test). Using logistic regression modeling, mean hearing level at the six frequencies was positively associated with a higher risk of cochlear ELH (odds ratio, 1.3; 95% confidence interval, 1.1–1.5 per 10-dB increment). In the same regression model, age did not impact the outcome of cochlear ELH (odds ratio, 1.0; 95%confidence interval, 0.7–1.4 per 10-year increment). Age did not differ among ears with no ELH (mean ± standard deviation age, 48.6 ± 14.4 yr), ears with only cochlear ELH (59.3 ± 10.7 yr), ears with only vestibular ELH (50.4 ± 16.9 yr), or ears with both cochlear and vestibular ELH (51.5 ± 18.4 yr; p > 0.05, analysis of variance).

Conclusion

Chronological age was not associated with the formation of ELH. Aging per se may not be associated with the development of ELH in neurotologic patients.
Matters of care and the good death – rhetoric or reality?
Authors: Collier Aileen , Chapman Michael
Published: July 2023

Purpose of review

The notion of a ‘good death’ is central to hospice and palliative care philosophy. This review interrogates social imaginaries of the ‘good death’ in the context of current global, health and sociopolitical challenges.

Recent findings

Research literature and policy documents across fields continue to place emphasis on the ‘good death’. As part of the equity turn in palliative care, there is a growing body of work highlighting the diverse perspectives of people whose voices were heretofore not understood. Inequities are evident not only in terms of who has access to a ‘good death’ but also related to the effects of the dominant ‘good death’ script itself.

There is increasing evidence that pursuit of the ‘good death’ narrative may be counter to supporting people as they are living and dying. The authors instead argue for a research, policy and practice shift to ‘matters of care’.
A multidrug-resistant Salmonella enterica Typhimurium DT104 complex lineage circulating among humans and cattle in the USA lost the ability to produce pertussis-like toxin ArtAB
Authors: Carroll Laura M. , Piacenza Nicolo , Cheng Rachel A. , Wiedmann Martin , Guldimann Claudia
Published: July 2023

Salmonella entericasubsp.entericaserotype Typhimurium definitive type 104 (DT104) can infect both humans and animals and is often multidrug-resistant (MDR). Previous studies have indicated that, unlike mostS. Typhimurium, the overwhelming majority of DT104 strains produce pertussis-like toxin ArtAB via prophage-encoded genesartAB. However, DT104 that lackartABhave been described on occasion. Here, we identify an MDR DT104 complex lineage circulating among humans and cattle in the USA, which lacksartAB(i.e. the ‘U.S.artAB-negative major clade’;n=42 genomes). Unlike most other bovine- and human-associated DT104 complex strains from the USA (n=230 total genomes), which harbourartABon prophage Gifsy-1 (n=177), members of the U.S.artAB-negative major clade lack Gifsy-1, as well as anti-inflammatory effectorgogB. The U.S.artAB-negative major clade encompasses human- and cattle-associated strains isolated from ≥11 USA states over a 20-year period. The clade was predicted to have lostartAB, Gifsy-1 andgogBcirca 1985–1987 (95 % highest posterior density interval 1979.0–1992.1). When compared to DT104 genomes from other regions of the world (n=752 total genomes), several additional, sporadicartAB, Gifsy-1 and/orgogBloss events among clades encompassing five or fewer genomes were observed. Using phenotypic assays that simulate conditions encountered during human and/or bovine digestion, members of the U.S.artAB-negative major clade did not differ from closely related Gifsy-1/artAB/gogB-harbouring U.S. DT104 complex strains (ANOVA rawP>0.05); thus, future research is needed to elucidate the roles thatartAB,gogBand Gifsy-1 play in DT104 virulence in humans and animals.
Production and performance assessment of a SARS-CoV-2 biomimetic in a verification program for pandemic readiness
Authors: Machowski Edith Erika , Reyneke Anna Esther , Sher Dean Evan , Kana Bavesh Davandra
Published: July 2023

During the early stages of the Covid-19 pandemic in South Africa, one of many challenges included availability of control material proficiency testing programs. Control material utilising live SARS-CoV-2 or RNA extracted from cell culture was either biohazardous and costly, particularly in resource limited settings. Here, we report the development and application of a non-infectious SARS-CoV-2 biomimeticMycobacterium smegmatisstrain that mimics a positive result in the GeneXpert SARS-CoV-2 Xpert Xpress cartridge. Nucleotide sequences located in genes encoding the RNA-dependent RNA polymerase, the nucleocapsid and the envelope proteins were used. The resulting biomimetic was prepared as a Quality Control specimen and distributed to laboratories in South Africa for validation prior to testing of clinical specimens. Between April 2020 and December 2020, a total of 151 instruments were validated to bring Covid-19 mass testing online. These instruments capacitated the country to perform tests in 2532 modules. False negative or false positive findings reflected issues such as workflow/technician error or other related technical issues. This non-infectious, easily scalable control material became available within two months after the start of the pandemic in South Africa and represents a useful approach to consider for other diseases and future pandemics.
First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction
Authors: Becerra-Fajardo Laura , Minguillon Jesus , Krob Marc Oliver , Rodrigues Camila , Sánchez Miguel González- , Megía-García Álvaro , Galán Carolina Redondo , Henares Francisco Gutiérrez , Comerma Albert , del-Ama Antonio J. , Gil-Agudo Angel , Grandas Francisco , Schneider-Ickert Andreas , Barroso Filipe Oliveira , Ivorra Antoni
Published: July 2023

Background

Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation.

Methods

A proof-of-concept device, consisting of implantable thin-film electrodes and a non-implantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant.

Results

Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device.

Conclusions

This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.
Non-invasive modulation of the human dorsal anterior cingulate attenuates acute pain perception and homeostatic cardiovascular responses
Authors: Strohman Andrew , Payne Brighton , In Alexander , Stebbins Katelyn , Legon Wynn
Published: July 2023

Homeostasis is the process of maintaining physiologic balance in the body that is critical for maintaining health and is dysfunctional in several disorders like chronic pain. The dorsal anterior cingulate cortex (dACC) is a critical brain area for homeostatic cardiovascular responses and pain processing, making it a promising non-invasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to non-invasively modulate the dACC for an effect on behavioral and cardiac autonomic responses using a transient heat pain stimulus. N = 16 healthy human volunteers (6M/10F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included perceived pain ratings, homeostatic measures including heart-rate variability, blood pressure, EDR response as well as the amplitude of the contact heat-evoked potential (CHEP).

LIFU reduced pain ratings by 1.08 ± 0.21 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on blood pressure or EDR. LIFU resulted in a 25.1% reduction in the N1-P1 CHEP amplitude driven primarily by effects on the P1 amplitude. Our results demonstrate LIFU to the dACC reduces perceived pain and alters homeostatic cardiovascular responses to a transient heat pain stimulus. These results have implications for the causal understanding of human pain and autonomic processing in the dACC and the potential for future therapeutics for pain relief and homeostatic modulation.

SIGNIFICANCE STATEMENT

New lines of inquiry now demonstrate cardiac homeostatic signals like heart rate variability (HRV) are aberrant in mental health disorders, addiction, and chronic pain and may contribute to their underlying etiology. The dorsal anterior cingulate cortex (dACC) is a key homeostatic center with direct influences on cardiovascular autonomic function, but its depth precludes direct access without invasive surgery. For the first time in humans, we demonstrate low-intensity focused ultrasound (LIFU) can non-invasively and selectively modulate the dACC to reduce acute pain perception and homeostatic cardiovascular responses as well as pain processing signals. This work helps establish a causal role of the dACC in pain perception and homeostatic signaling with potential future clinical applications in chronic pain and neuropsychological populations.
Both systemic Calcitonin Gene Related Peptide (CGRP) and a vestibular challenge promote anxiety-related behaviors and dynamic imbalance in mice
Authors: Rahman Shafaqat M. , Hauser Catherine , Faucher Stefanie , Fine Elana , Luebke Anne E.
Published: July 2023

Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and vestibular migraine, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel (r = 1.5 cm) versus rat dowel (r = 3.5 cm). EPM results indicate CGRP increased anxiety indexes and time spent in the closed arms in females but not males, while OVAR increased anxiety indexes and time spent in the closed arms in both sexes. The combination of CGRP and OVAR elicited even greater anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. Rotarod performance is influenced by dowel diameter, with larger dowels presenting greater challenges on balance function. These results suggest that both CGRP and vestibular stimulation induce anxiety-like behavior and that CGRP affects dynamic balance function in mice depending on the type of challenge presented. Findings highlight the potential translation of anti-CGRP receptor signaling therapeutics for treating motion hypersensitivity and motion-induced anxiety that manifests in vestibular migraine.

Significance statement

Anxiety is very common in patients with dizziness and vestibular migraine (VM). Elevated CGRP levels have been linked to migraine symptoms of increased light and touch sensitivity in mice and humans and we wondered if a systemic injection of CGRP into mice would increase anxiety and imbalance; and if mice further exposed to a vestibular stimulus would have their anxiety measures sharpened. We observed a female preponderance in both CGRP and motion-induced anxiety-like behaviors, suggesting that the role of CGRP in migraine’s anxiety symptoms can be recapitulated in the mouse. Our findings suggest that CGRP signaling has a pertinent role in motion-induced anxiety and dynamic imbalance, and warrants the potential use of anti-CGRP therapies for the treatment of these symptoms.
Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants
Authors: Mühlemann Barbara , Trimpert Jakob , Walper Felix , Schmidt Marie L. , Schroeder Simon , Jeworowski Lara M. , Beheim-Schwarzbach Jörn , Bleicker Tobias , Niemeyer Daniela , Adler Julia M. , Vidal Ricardo Martin , Langner Christine , Vladimirova Daria , Smith Derek J. , Voß Mathias , Paltzow Lea , Martínez Christophersen Christina , Rose Ruben , Krumbholz Andi , Jones Terry C. , Corman Victor M. , Drosten Christian
Published: July 2023

SARS-CoV-2 has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of eight SARS-CoV-2 variants. Their sera were titrated against 14 SARS-CoV-2 variants and the resulting titers visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant), and a considerably more distributed positioning among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/5, the BA.5 descendants BF.7 and BQ.1.18; the BA.2.75 descendant BN.1.3.1; and the BA.2-derived recombinant XBB.2). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. The results highlight the potential of using variant-specifically infected hamster sera for the continued antigenic characterisation of SARS-CoV-2.
Lack of detection of SARS-CoV-2 in Wildlife from Kerala, India in 2020-21
Authors: Zachariah Arun , Krishnankutty Sajesh P , Manazhi Jishnu , Omanakuttan Vishnu , Santhosh Sam , Blanchard Adam , Tarlinton Rachael
Published: July 2023

2.

Spill over of SARs-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white tailed deer in North America and increasing divergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121Rhinolophus rouxii(Rufous Horsehoe Bat),6 Rhinolophus bedommei(Lesser Woolly Horseshoe Bat),15 Rossettus leschenaultii(Fulvous Fruit Bat),47 Macaca radiata(Bonnet macaques),35 Paradoxurus hermaphroditus (Common Palm Civet),5 Viverricula indica(Small Indian Civet),4 Herpestes edwardsii(Common Mongoose),10 Panthera tigris(Bengal Tiger),8 Panthera pardus fusca(Indian Leopard), 4Prionailurus bengalensis(Leopard cats), 2Felis chaus(Jungle cats), 2Cuon alpinus(Wild dogs) and 1Melursus ursinus(sloth bear).