bluuebunny/crossref_metadata_2025 huggingface dataset:
Long day for few hours: impact of working time fragmentation on low wages in France
Authors: Devetter François-Xavier , Valentin Julie
Published: December 2023

Since the 1980s, working hours have tended to become more diverse and flexible. These developments impact not only the possibilities of synchronising social time but also pay levels. Duration indicators become less relevant, since they disconnect the time worked and paid from the impact of the work on employees’ lives. The objective of this paper is to analyse the effects of this disconnection by measuring the fragmentation of the working day. We propose an indicator of ‘density of daily working time’ which links two specific durations (the extent of the working day and the average daily duration of working). This indicator shows that a low density of the working day makes it possible to circumvent the minimum wage principle, particularly in the case of lower-skilled service occupations. These results raise questions about how working time is measured and about its regulation.
An intuitive method to reduce the defibrillation threshold: a case report
Authors: Chaudry Hayyan Asim , Maskoun Waddah
Published: December 2023

Background

Defibrillation threshold (DFT) testing is done to assess whether proper sensing of ventricular fibrillation and adequate safety margin for defibrillation are present in an implantable cardioverter defibrillator (ICD). This case report presents an intuitive method for lowering the DFT. It may be used on a larger scale in other patients with high DFTs when other methods for lowering the DFT (changing medications, adjusting the device, and adding coils) are not feasible or preferable to use.

Case summary

A 64-year-old male presented to the emergency room with failed appropriate shocks from his ICD. Device interrogation revealed that he failed his first maximum output shock before subsequent shock at the same polarity and output succeeded, suggesting a high DFT. Therefore, the DFT needs to be lowered in our patient. After considering the potential efficacy and risk of a number of traditional options, we used an intuitive method whereby the right ventricular (RV) coils of two separate leads were combined via a y-adapter. This method successfully lowered the patient’s DFT, and he received successful shocks from his ICD over the next 9 months before reaching end-stage heart failure. He received a transplant, and the device and transvenous leads, except for the superior vena cava coil, were successfully removed.

Discussion

Combining two RV coils from different locations may lower the DFT. This method may be considered in the larger population in cases where using traditional methods are not safe or possible for certain patients. This method may work by lowering shock impedance and increasing the shock tissue surface area.
Right ventricular to pulmonary arterial coupling in patients with repaired tetralogy of Fallot: a case series
Authors: Joosen Renée S , Breur Johannes M P J , Wessels Jeroen N , Krings Gregor J , Voskuil Michiel , de Man Frances S , van de Veerdonk Marielle C
Published: December 2023

Background

In repaired tetralogy of Fallot (ToF) patients with residual right ventricular (RV) outflow tract obstructions (RVOTO), risk stratification and timing of re-interventions are based on RVOTO gradients. However, this might be insufficient to prevent RV dysfunction. Instead, assessment of RV to pulmonary arterial (RV-PA) coupling allows integrated assessment of RV function in relationship to its afterload and could be of additional value in clinical decision-making.

Case summary

Two patients with repaired ToF and residual RVOTO without pulmonary regurgitation underwent right heart catheterization (RHC) and cardiac magnetic resonance imaging. We determined RV end-systolic elastance (Ees), arterial elastance (Ea) and RV-PA coupling (Ees/Ea) using single-beat RV pressure–volume analysis. Patient 1 was asymptomatic despite severely increased RV pressures and a left pulmonary artery (LPA) stenosis (invasive gradient 20 mmHg). Right ventricular volumes and function were preserved. The Ea and Ees were increased but RV-PA coupling was relatively maintained. Of interest, RV end-diastolic pressure and RV diastolic stiffness were increased. After LPA plasty, RV function was preserved during long-term follow-up. Patient 2 was symptomatic despite mildly elevated RV pressures and a supravalvular RV-PA conduit stenosis (invasive gradient 30 mmHg). The RV showed severe RV dilatation and dysfunction. The Ea was increased but Ees was decreased leading to RV-PA uncoupling. Despite balloon angioplasty, RV function was unchanged during long-term follow-up.

Discussion

Development of RV dysfunction might be insufficiently predicted by RVOTO severity in patients with repaired ToF. Assessment of RV remodelling and function in relationship to its afterload might help to optimize risk stratification.
Fully magnetically centrifugal left ventricular assist device and long-term outcomes: the ELEVATE registry
Authors: Schmitto Jan D , Shaw Steven , Garbade Jens , Gustafsson Finn , Morshuis Michiel , Zimpfer Daniel , Lavee Jacob , Pya Yuriy , Berchtold-Herz Michael , Wang AiJia , Gazzola Carlo , Potapov Evgenij , Saeed Diyar
Published: December 2023

Background and Aims

HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval.

Methods

A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival.

Results

Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1–3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively).

Conclusions

Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure.
Wild bee and pollen microbiomes across an urban–rural divide
Authors: Nguyen Phuong N , Rehan Sandra M
Published: December 2023

Wild pollinators and their microbiota are sensitive to land use changes from anthropogenic activities that disrupt landscape and environmental features. As urbanization and agriculture affect bee habitats, human-led disturbances are driving changes in bee microbiomes, potentially leading to dysbiosis detrimental to bee fitness. This study examines the bacterial, fungal, and plant compositions of the small carpenter bee, Ceratina calcarata, and its pollen provisions across an urban–rural divide. We performed metabarcoding of C. calcarata and provisions in Toronto by targeting the 16S rRNA, ITS, and rbcL regions. Despite similar plant composition and diversity across bees and their provisions, there was a greater microbial diversity in pollen provisions than in bees. By characterizing the differences in land use, climate, and pesticide residues that differentiate urban and rural landscapes, we find that urban areas support elevated levels of microbial diversity and more complex networks between microbes and plants than rural areas. However, urban areas may lead to lower relative abundances of known beneficial symbionts and increased levels of pathogens, such as Ascosphaera and Alternaria fungi. Further, rural pollen provisions indicate elevated pesticide residues that may dysregulate symbiosis. As anthropogenic activities continue to alter land use, ever changing environments threaten microbiota crucial in maintaining bee health.
Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults: A Post Hoc Analysis of ASPREE Trial
Authors: Zhou Zhen , Tonkin Andrew M , Curtis Andrea J , Murray Anne , Zhu Chao , Reid Christopher M , Williamson Jeff D , Ryan Joanne , McNeil John J , Beilin Lawrence J , Ernst Michael E , Stocks Nigel , Lacaze Paul , Shah Raj C , Woods Robyn L , Wolfe Rory , Gall Seana , Zoungas Sophia , Orchard Suzanne G , Nelson Mark R
Published: December 2023

Background

The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals.

Methods

This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models.

Results

We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3–3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (pinteraction < .05).

Conclusions

There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results.
Association Between Trajectory of Socioeconomic Position and Regional Brain Volumes Related to Dementia: Results From the NEIGE Study
Authors: Morita Ayako , Fujiwara Takeo , Murayama Hiroshi , Machida Masaki , Inoue Shigeru , Shobugawa Yugo
Published: December 2023

Background

Low socioeconomic position (SEP) has been linked to an increased risk of dementia. However, little is known about the association between SEP trajectory and regional brain volumes related to dementia.

Methods

A random sample of community-dwelling older adults (n = 428, age = 73.1 ± 5.5) living in Tokamachi City (Niigata Prefecture, Japan) without medical histories of dementia, Parkinson’s disease, and depression who underwent automated assessment of brain volumes on magnetic resonance imaging and responded to a self-administered questionnaire survey in 2017. We measured SEP in childhood (household SEP at age 15), young adulthood (education), mid-adulthood (the longest occupation), and late adulthood (current wealth), and further performed group-based trajectory analysis to identify lifetime trajectory patterns on SEP. Multivariate regression models were employed to investigate the association between SEP trajectories and 4 regional brain volumes related to the development of Alzheimer’s disease (ie, entorhinal cortex, hippocampus, amygdala, and the parahippocampus), the most common type of dementia.

Results

We found 3 distinct SEP trajectories (stable middle class [68%], downward [23%], and upward [9%]). Compared to those who experienced stable middle class, older adults who experienced the upward SEP mobility had significantly larger hippocampus (β: 213.2, 95% confidence interval: 14.7, 411.8). On the other hand, older adults who experienced downward SEP mobility showed no significant differences in any of the 4 brain structural volumes.

Conclusions

Our findings indicate that upward life-course SEP mobility is associated with larger volumes of hippocampus in old age. SEP trajectory may offer us a useful lens to enhance our understanding of the etiology of dementia.
Prescription drug monitoring program use by opioid prescribers: a cross-sectional study
Authors: Sacarny Adam , Williamson Ian , Merrick Weston , Avilova Tatyana , Jacobson Mireille
Published: December 2023

Clinician use of prescription drug monitoring programs (PDMPs) has been linked to better patient outcomes, but state requirements to use PDMPs are unevenly enforced. We assessed PDMP use in Minnesota, which requires opioid prescribers to hold accounts and, in most cases, search the PDMP before prescribing, but where enforcement authority is limited. Using 2023 PDMP data, we found that 4 in 10 opioid prescribers did not search and 2 in 10 did not hold an account. PDMP use was strongly associated with prescribing volume, but even among the top decile of opioid prescribers, 8% never searched the PDMP. Thirty-two percent of opioid fills came from clinicians who did not search the PDMP. Failures to use the PDMP may be driven by a lack of information about state requirements, beliefs that these requirements are not enforced, and the costs of accessing the PDMP relative to the benefits. These results highlight the potential for policy makers to promote safer and better-informed prescribing of opioids and other drugs by addressing the forces that have limited PDMP use so far.
Geographic variations in driving time to US mental health care, digital access to technology, and household crowdedness
Authors: Negaro Sophia N D , Hantman Rachel M , Probst Janice C , Crouch Elizabeth L , Odahowski Cassie L , Andrews Christina M , Hung Peiyin
Published: December 2023

Rural residents face significant barriers in accessing mental health care, particularly as the demand for such services grows. Telemedicine has been proposed as an answer to rural gaps, but this service requires both access to appropriate technology and private space in the home to be useful. Our study documented longer travel time to mental health facilities in rural areas and greater barriers to digital devices for telemedicine access in those same areas. However, urban areas demonstrated greater household crowdedness than rural noncore areas when looking at private space within the home. Across ZIP Code Tabulation Areas located more than an estimated 30 minutes from the nearest outpatient care, 675 950 (13.1%) rural households vs 329 950 (6.4%) urban households had no broadband internet. The current Affordable Connectivity Program should target mental health–underserved communities, especially in rural America, where the scarcity of digital access compounds travel burdens to mental health care.
MiR-182-5p: A Novel Biomarker in the Treatment of Depression in CSDS-Induced Mice
Authors: Zheng Ya-Bin , Sheng Xiao-Ming , Jin Xiang , Guan Wei
Published: December 2023

Background

Depression is a neuropsychiatric disease with a high disability rate and mainly caused by the chronic stress or genetic factors. There is increasing evidence that microRNAs (miRNAs) play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far.

Methods

We first established a chronic social defeat stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs suggested in previous reports to be involved in depression and found miR-182-5p was selected as a candidate for analysis in the hippocampus. Then western blotting and immunofluorescence were used together to examine whether adeno-associated virus (AAV)-siR-182-5p treatment alleviated chronic stress–induced decrease in hippocampal Akt/GSK3β/cAMP-response element binding protein (CREB) signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, CREB inhibitor was adopted to examine if blockade of Akt/GSK3β/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice.

Results

Knockdown of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in behavioral testing and neuronal neurogenesis within hippocampus of mice.

Conclusions

These findings indicated that hippocampal miR-182-5p/Akt/GSK3β/CREB signaling pathway participated in the pathogenesis of depression, and it might give more opportunities for new drug developments based on the miRNA target in the clinic.
Evaluation of prescription review and feedback policy on rational antibiotic use in primary healthcare settings in Beijing, China: a qualitative study using the Theoretical Domains Framework and the behaviour change wheel
Authors: Wushouer Haishaerjiang , Du Kexin , Chen Shicai , Li Huangqianyu , Zhang Wanmeng , Yang Yaoyao , Hu Lin , Zhou Yue , Sun Hui , Zheng Bo , Guan Xiaodong , Shi Luwen
Published: December 2023

Objectives

To decelerate antibiotic resistance driven by inappropriate antibiotic prescribing, a prescription review and feedback (PRF) policy is implemented in primary healthcare institutions (PHIs) in Beijing, China. However, evaluation of PRF implementation in PHIs is scarce. This study aims to systematically identify the barriers and facilitators of PRF policy implementation to provide evidence for antimicrobial stewardship.

Methods

We conducted key informant interviews with 40 stakeholders engaged in the implementation of PRF in Beijing, including physicians, pharmacists and administrators. Interviews were audio recorded and transcribed verbatim. We coded the interview transcripts and mapped informant views to domains of the Theoretical Domains Framework. We then used a behaviour change wheel to suggest possible behavioural interventions.

Results

Procedural knowledge (Knowledge) and skills (Skill) of PRF were possessed by stakeholders. They felt responsible to promote the appropriate use of antibiotics (Social/professional role and identity) and believed that PRF could help to change inappropriate provider behaviours (Behavioural regulation) in prescribing antibiotics (Beliefs about consequences) under increased intention on antibiotic use (Stages of change). Moreover, informants called for a more unified review standard to enhance PRF implementation (Goals). Frequently identified barriers to PRF included inadequate capacity (Skill), using punishment mechanism (Behaviour regulation), reaching consistently lower antibiotic prescription rates (Goals), lack of resources (Environmental context and resources) and perceived pressure coming from patients (Social influences).

Conclusions

Stakeholders believed that PRF implementation promoted the rational use of antibiotics at PHIs in Beijing. Still, PRF was hampered by inconsistencies in review process and resources needed for PRF implementation.
Methods for studying medication safety following electronic health record implementation in acute care: a scoping review
Authors: Pereira Nichole , Duff Jonathan P , Hayward Tracy , Kherani Tamizan , Moniz Nadine , Champigny Chrystale , Carson-Stevens Andrew , Bowie Paul , Egan Rylan
Published: December 2023

Objectives

The objective of this scoping review is to map methods used to study medication safety following electronic health record (EHR) implementation. Patterns and methodological gaps can provide insight for future research design.

Materials and methods

We used the Joanna Briggs Institute scoping review methodology and a custom data extraction table to summarize the following data: (1) study demographics (year, country, setting); (2) study design, study period, data sources, and measures; (3) analysis strategy; (4) identified limitations or recommendations; (5) quality appraisal; and (6) if a Safety-I or Safety-II perspective was employed.

Results

We screened 5879 articles. One hundred and fifteen articles met our inclusion criteria and were assessed for eligibility by full-text review. Twenty-seven articles were eligible for extraction.

Discussion and conclusion

We found little consistency in how medication safety following EHR implementation was studied. Three study designs, 7 study settings, and 10 data sources were used across 27 articles. None of the articles shared the same combination of design, data sources, study periods, and research settings. Outcome measures were neither defined nor measured consistently. It may be difficult for researchers to aggregate and synthesize medication safety findings following EHR implementation research. All studies but one used a Safety-I perspective to study medication safety. We offer a conceptual model to support a more consistent approach to studying medication safety following EHR implementation.
Digital Breast Tomosynthesis With Synthetic Mammography: Are We Missing Calcifications That Matter?
Authors: Nguyen Adrien , Mirchandani Anicia , Joseph Sumita , Mapkar Zaiba , Singh Evita
Published: December 2023

Objective

To determine whether there are differences in the biopsy outcomes for suspicious calcifications detected with screening mammography using the digital breast tomosynthesis and synthetic 2D (DBT/SM) technique compared to calcifications detected using the full-field digital (DM) technique.

Methods

This retrospective study was IRB approved. The records for all stereotactic biopsies performed for suspicious calcifications detected on screening mammograms using DM in 2011–2014 and DBT/SM in 2017–2020 were reviewed. We collected patient, imaging, and pathology data from the breast imaging database and from retrospective review of a subset of mammograms. The biopsy outcome results were categorized as benign, benign with upgrade potential (BWUP), and malignant based on final pathology. Frequencies and proportions of outcomes were calculated and compared using Mann-Whitney U tests and Wilcoxson signed-rank tests with P-values and 95% confidence intervals (95% CIs).

Results

From 2011 to 2014 (DM), 1274 stereotactic biopsies of calcifications yielded 74.2% (945/1274) benign, 11.5% (147/1274) BWUP, and 14.3% (182/1274) malignant outcomes. From 2017 to 2020 (DBT/SM), 1049 stereotactic biopsies yielded 65.2% (684/1049) benign, 15.6% (164/1049) BWUP, and 19.2% (201/1049) malignant outcomes. With DBT/SM, benign biopsy outcomes decreased (9.0%, 95% CI 0.87–11.53, P < 0.05), whereas malignant biopsy outcomes increased (4.9%, 95% CI 0.94–8.36, P < 0.05). There was no significant difference in BWUP biopsy outcomes and total biopsy rates between techniques (P > 0.05).

Conclusion

Calcifications detected with screening DBT/SM technique were significantly more likely to be malignant than those found using DM. These results support using the DBT/SM technique without obtaining concurrent DM images.
Surfing the Korean Wave
Authors: Goldsmith Robyn
Published: December 2023

Watched Squid Game, heard BTS or eaten ramyeon? You might be “Kontagious”. In her winning entry for our 2023 Statistical Excellence Award for Early Career Writing, Robyn Goldsmith takes a statistician's view of Korean culture's astonishing recent rise in international popularity
Starbursts driven by central gas compaction
Authors: Cenci Elia , Feldmann Robert , Gensior Jindra , Moreno Jorge , Bassini Luigi , Bernardini Mauro
Published: December 2023

Starburst (SB) galaxies are a rare population of galaxies with star formation rates (SFRs) greatly exceeding those of the majority of star-forming galaxies with similar stellar mass. It is unclear whether these bursts are the result of either especially large gas reservoirs or enhanced efficiencies in converting gas into stars. Tidal torques resulting from gas-rich galaxy mergers are known to enhance the SFR by funnelling gas towards the centre. However, recent theoretical works show that mergers do not always trigger an SB and not all SB galaxies are interacting systems, raising the question of what drives an SB. We analyse a large sample of SB galaxies and a mass- and redshift-matched sample of control galaxies, drawn from the FIREbox cosmological volume at z = 0–1. We find that SB galaxies have both larger molecular gas fractions and shorter molecular depletion times than control galaxies, but similar total gas masses. Control galaxies evolve towards the SB regime by gas compaction in their central regions, over time-scales of ∼70 Myr, accompanied by an increase in the fraction of ultradense and molecular gas. The driving mechanism behind the SB varies depending on the mass of the galaxy. Massive ($M_\star \gtrsim 10^{10}~\rm {M}_\odot$) galaxies undergoing intense, long-lasting SBs are mostly driven by galaxy interactions. Conversely, SBs in non-interacting galaxies are often triggered by a global gravitational instability, which can result in a ‘breathing’ mode in low-mass galaxies.
Jellyfish galaxies with the IllustrisTNG simulations – citizen-science results towards large distances, low-mass hosts, and high redshifts
Authors: Zinger Elad , Joshi Gandhali D , Pillepich Annalisa , Rohr Eric , Nelson Dylan
Published: December 2023

We present the ‘Cosmological Jellyfish’ project – a citizen-science classification program to identify jellyfish (JF) galaxies within the IllustrisTNG cosmological simulations. JF are satellite galaxies that exhibit long trailing gas features – ‘tails’ – extending from their stellar body. Their distinctive morphology arises due to ram-pressure stripping (RPS) as they move through the background gaseous medium. Using the TNG50 and TNG100 simulations, we construct a sample of $\sim 80\, 000$ satellite galaxies spanning an unprecedented range of stellar masses, $10^{8.3}{-}10^{12.3}\, \mathrm{M_\odot }$, and host masses, $M_\mathrm{200,c}=10^{10.4}{-}10^{14.6}\, \mathrm{M_\odot }$ back to z = 2. Based on this sample, $\sim 90\, 000$ galaxy images were presented to volunteers in the citizen-science Zooniverse platform, who were asked to determine whether the galaxy image resembles a JF. Based on volunteer votes, each galaxy received a score determining if it is a JF or not. This paper describes the project, the inspected satellite sample, the methodology, and the classification process that resulted in a data set of 5307 visually identified JF galaxies. We find that JF is common in nearly all group- and cluster-sized systems, with the JF fraction increasing with host mass and decreasing with satellite stellar mass. We highlight JF galaxies in three relatively unexplored regimes: low-mass hosts of $M_\mathrm{200,c}\sim 10^{11.5}{-}10^{13}\, \mathrm{M_\odot }$, radial positions within hosts exceeding the virial radius R200, c, and at high redshift up to z = 2. The full data set of our JF scores is publicly available and can be used to select and study JF galaxies in the IllustrisTNG simulations.
Impact of More Intense Smoking Parameters and Flavor Variety on Toxicant Levels in Emissions of a Heated Tobacco Product
Authors: Davigo Michele , Klerx Walther N M , van Schooten Frederik-Jan , Opperhuizen Antoon , Remels Alexander H V , Talhout Reinskje
Published: December 2023

Introduction

IQOS HEETS are promoted as reduced-risk alternatives to cigarettes. Although some studies have investigated the chemical composition of HEETS emissions, little is known on whether toxicant levels in such emissions are affected by different puffing parameters and flavor varieties. This has important implications when assessing actual human exposure, since IQOS users develop a specific and personalized puffing behavior and may use different HEETS variants.

Methods

This study measured the levels of nicotine, total particulate matter, carbonyl compounds, and tobacco-specific nitrosamines (TSNAs) in the emissions of nine differently flavored HEETS and two cigarettes (1R6F and Marlboro Red, MR). Emissions from Yellow HEETS, 1R6F, and MR were collected using the World Health Organization Intense smoking regime and four more intense smoking regimes.

Results

Yellow HEETS aerosol contained lower levels of toxicants compared to 1R6F and MR smoke. More intense smoking regimes increased carbonyl release in cigarette smoke, whereas only higher puff frequency led to lower levels of toxicants in Yellow HEETS aerosol. Some HEETS varieties exhibited higher levels of formaldehyde and TSNAs in their aerosols compared to Yellow HEETS.

Conclusions

Puff frequency was identified as the only smoking parameter that significantly lowered the release of almost all toxicants in Yellow HEETS, whereas a combination of higher puff volume and puff duration led to increased levels of some carbonyls. Differences in toxicant levels between various commercially available HEETS have important implications when assessing their health impact, as their consumption might induce different toxicant exposure and health effects.

Implications

HEETS release about half as much nicotine and substantially lower levels of toxicants compared to cigarettes. Literature data showed that puffing intensity is increased in cigarette smokers switching to HEETS, maybe in reaction to these lower nicotine levels. Our results show a differential impact of increased puff frequency, puff duration, and puff volume in the release of toxicants from HEETS. Thus, industry-independent studies on puff topography are critical to make choices for the most relevant puffing regime for heated tobacco product regulation. Regulators should consider evaluating the health impact of multiple HEETS varieties, as the tobacco filler composition significantly affects the release of certain toxicants.
Forces driving transposable element load variation during Arabidopsis range expansion
Authors: Jiang Juan , Xu Yong-Chao , Zhang Zhi-Qin , Chen Jia-Fu , Niu Xiao-Min , Hou Xing-Hui , Li Xin-Tong , Wang Li , Zhang Yong E , Ge Song , Guo Ya-Long
Published: December 2023

Genetic load refers to the accumulated and potentially life-threatening deleterious mutations in populations. Understanding the mechanisms underlying genetic load variation of transposable element (TE) insertion, a major large-effect mutation, during range expansion is an intriguing question in biology. Here, we used 1,115 global natural accessions of Arabidopsis (Arabidopsis thaliana) to study the driving forces of TE load variation during its range expansion. TE load increased with range expansion, especially in the recently established Yangtze River basin population. Effective population size, which explains 62.0% of the variance in TE load, high transposition rate, and selective sweeps contributed to TE accumulation in the expanded populations. We genetically mapped and identified multiple candidate causal genes and TEs, and revealed the genetic architecture of TE load variation. Overall, this study reveals the variation in TE genetic load during Arabidopsis expansion and highlights the causes of TE load variation from the perspectives of both population genetics and quantitative genetics.
Transcription factors BZR2/MYC2 modulate brassinosteroid and jasmonic acid crosstalk during pear dormancy
Authors: Wang Xuxu , Wei Jia , Wu Jiahao , Shi Baojing , Wang Peihui , Alabd Ahmed , Wang Duanni , Gao Yuhao , Ni Junbei , Bai Songling , Teng Yuanwen
Published: December 2023

Bud dormancy is an important physiological process during winter. Its release requires a certain period of chilling. In pear (Pyrus pyrifolia), the abscisic acid (ABA)-induced expression of DORMANCY-ASSOCIATED MADS-box (DAM) genes represses bud break, whereas exogenous gibberellin (GA) promotes dormancy release. However, with the exception of ABA and GA, the regulatory effects of phytohormones on dormancy remain largely uncharacterized. In this study, we confirmed brassinosteroids (BRs) and jasmonic acid (JA) contribute to pear bud dormancy release. If chilling accumulation is insufficient, both 24-epibrassinolide (EBR) and methyl jasmonic acid (MeJA) can promote pear bud break, implying that they positively regulate dormancy release. BRASSINAZOLE RESISTANT 2 (BZR2), which is a BR-responsive transcription factor, inhibited PpyDAM3 expression and accelerated pear bud break. The transient overexpression of PpyBZR2 increased endogenous GA, JA, and JA-Ile levels. In addition, the direct interaction between PpyBZR2 and MYELOCYTOMATOSIS 2 (PpyMYC2) enhanced the PpyMYC2-mediated activation of Gibberellin 20-oxidase genes PpyGA20OX1L1 and PpyGA20OX2L2 transcription, thereby increasing GA3 contents and accelerating pear bud dormancy release. Interestingly, treatment with 5 μm MeJA increased the bud break rate, while also enhancing PpyMYC2-activated PpyGA20OX expression and increasing GA3,4 contents. The 100 μm MeJA treatment decreased the PpyMYC2-mediated activation of the PpyGA20OX1L1 and PpyGA20OX2L2 promoters and suppressed the inhibitory effect of PpyBZR2 on PpyDAM3 transcription, ultimately inhibiting pear bud break. In summary, our data provide insights into the crosstalk between the BR and JA signaling pathways that regulate the BZR2/MYC2-mediated pathway in the pear dormancy release process.
Frederik W. de Klerk: Presidential Years in the International Arena
Authors: Eksteen Riaan
Published: December 2023

In South Africa's history, Frederik W. de Klerk has left numerous bookmarks. During his presidency (1989-1994), notable ones relate to his handling of foreign affairs. When he became president, he was a novice in this field. His reputation at home was initially built on conservative values. When he succeeded Pieter W. Botha in August 1985, South Africa was internationally isolated and internally in disarray. The date 2 February 1990, when he released Nelson Mandela from prison and unbanned the African National Congress (ANC) and the South African Communist Party (SACP), will forever be associated with an acclaimed and courageous political quantum leap. Soon afterwards, on 21 March 1990, he transferred South Africa's control and administration of Namibia to its first president. De Klerk dealt with two crucial issues head-on. First, he returned the military to true and proper civilian control. His decision to destroy South Africa's nuclear arsenal led to the signing of the Non-Proliferation of Nuclear Weapons Treaty in July 1991. By engaging in personal diplomacy, he forged remarkable relationships with President George H. W. Bush and Prime Minister Margaret Thatcher, who, together with other world leaders, recognized that De Klerk was determined to repair South Africa's disastrous foreign relations. He evaluated the events in Eastern Europe, the fall of the Berlin Wall, and demise of the Soviet Union in their proper context. In December 1993, he shared the Nobel Peace Prize with Mandela. Up to now De Klerk legacy in the realm of international relations have not been properly explored.
Robust Phylogenetic Regression
Authors: Adams Richard , Cain Zoe , Assis Raquel , DeGiorgio Michael
Published: December 2023

Modern comparative biology owes much to phylogenetic regression. At its conception, this technique sparked a revolution that armed biologists with phylogenetic comparative methods (PCMs) for disentangling evolutionary correlations from those arising from hierarchical phylogenetic relationships. Over the past few decades, the phylogenetic regression framework has become a paradigm of modern comparative biology that has been widely embraced as a remedy for shared ancestry. However, recent evidence has shown doubt over the efficacy of phylogenetic regression, and PCMs more generally, with the suggestion that many of these methods fail to provide an adequate defense against unreplicated evolution—the primary justification for using them in the first place. Importantly, some of the most compelling examples of biological innovation in nature result from abrupt lineage-specific evolutionary shifts, which current regression models are largely ill equipped to deal with. Here we explore a solution to this problem by applying robust linear regression to comparative trait data. We formally introduce robust phylogenetic regression to the PCM toolkit with linear estimators that are less sensitive to model violations than the standard least-squares estimator, while still retaining high power to detect true trait associations. Our analyses also highlight an ingenuity of the original algorithm for phylogenetic regression based on independent contrasts, whereby robust estimators are particularly effective. Collectively, we find that robust estimators hold promise for improving tests of trait associations and offer a path forward in scenarios where classical approaches may fail. Our study joins recent arguments for increased vigilance against unreplicated evolution and a better understanding of evolutionary model performance in challenging—yet biologically important—settings.
TRIM26 restricts Epstein–Barr virus infection in nasopharyngeal epithelial cells through K48‐linked ubiquitination of HSP‐90β
Authors: Zhang Mingjiao , Tan Haiqi , Gong Yibing , Faleti Oluwasijibomi Damola , Li Dengke , Yang Jinlong , Huang Jing , Long Jingyi , Luo Qingshuang , Wu Gongfa , Zheng Lei , Lyu Xiaoming
Published: December 2023

The tripartite interaction motif (TRIM) family of proteins is known for their antiviral activity through different mechanisms, such as interfering with viral components, regulating immune responses, and participating in autophagy‐mediated defense pathways. In this study, we investigated the role of tripartite interaction motif 26 (TRIM26), which is encoded by a major histocompatibility complex (MHC) gene, in regulating Epstein–Barr virus (EBV) infection of nasopharyngeal epithelial cells. We found that TRIM26 expression was induced upon EBV infection and that it indirectly targeted EphA2, a crucial epithelial receptor for EBV entry. Our results showed that TRIM26 interacted with heat shock protein 90‐beta (HSP‐90β) and promoted its polyubiquitination, which led to its degradation via the proteasome pathway. This, in turn, affected EphA2 integrity and suppressed EBV infection. These findings suggest that TRIM26 could be a valuable target for developing therapeutic interventions against EBV infection and its associated pathogenesis.
VNS‐mediated α7nAChR signaling promotes SPM synthesis via regulation of netrin‐1 expression during LPS‐induced ALI
Authors: Huang Yan , Dong Shuan , Li Xiangyun , Shi Jia , Zhang Yuan , Liu Shasha , Zhang Ye , Yu Jianbo
Published: December 2023

The α7 nicotinic acetylcholine receptor (α7nAChR) plays a crucial role in the cholinergic anti‐inflammatory pathway (CAP) during sepsis‐associated acute lung injury (ALI). Increasing evidence suggests that specialized pro‐resolving mediators (SPMs) are important in resolving α7nAChR‐mediated ALI resolution. Our study aims to elucidate the pivotal role of α7nAChR in the CAP during LPS‐associated acute lung injury (ALI). By employing vagus nerve stimulation (VNS), we identified α7nAChR as the key CAP subunit in ALI mice, effectively reducing lung permeability and the release of inflammatory cytokines. We further investigated the alterations in SPMs regulated by α7nAChR, revealing a predominant synthesis of lipoxin A4 (LXA4). The significance of α7nAChR‐netrin‐1 pathway in governing SPM synthesis was confirmed through the use of netrin‐1 knockout mice and siRNA‐transfected macrophages. Additionally, our evaluation identified a synchronous alteration of LXA4 synthesis in the α7nAChR‐netrin‐1 pathway accompanied by 5‐lipoxygenase (5‐LOX), thereby confirming an ameliorative effect of LXA4 on lung injury and macrophage inflammatory response. Concurrently, inhibiting the function of LXA4 annulled the lung‐protective effect of VNS. As a result, our findings reveal a novel anti‐inflammatory pathway wherein VNS modulates netrin‐1 expression via α7nAChR, ultimately leading to LXA4 synthesis and subsequent lung protection.
Remimazolam Dosing for Gastroscopy: A Randomized Noninferiority Trial
Authors: Zhu Huichen , Su Zhongxue , Zhou Hongmei , Lu Jian , Wang Xiangrui , Ji Zhonghua , Chen Shibiao , Wang Xiuhong , Yao Ming , Lu Yaping , Yu Weifeng , Su Diansan
Published: December 2023

Background

Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy.

Methods

This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety.

Results

The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, −0.64%; 97.5% CI, −2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, −10.8%; 97.5% CI, −14.0% to −8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group.

Conclusions

This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.

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Systemic Hypertension and Postoperative Symptomatic Spinal Epidural Hematoma: A Scoping Review
Authors: Robinson Lewis , Forget Patrice , Nesvadba David
Published: December 2023

Postoperative symptomatic spinal epidural hematoma (PSSEH) is a serious complication of spinal surgery that is associated with significant morbidity. Studies suggest that hypertension is a risk factor for the development of PSSEH. The aim of this review was to evaluate the literature reporting associations between hypertension and PSSEH. A comprehensive literature search was conducted using the MEDLINE/PubMed, Embase, and Cochrane Library databases to identify studies that investigated PSSEH and reported data on preoperative hypertension status and/or perioperative blood pressure (BP). Eighteen studies were identified for inclusion in the review. Observational data suggested that uncontrolled/untreated preoperative hypertension, extubation-related increases in systolic BP, and elevated postoperative systolic BP were associated with an increased risk of PSSEH. The overall quality of evidence was low because of the retrospective nature of the studies, heterogeneity, and lack of precision in reporting. Despite the limitations of the current evidence, our findings could be important in establishing preoperative BP targets for elective spine surgery and inform perioperative clinical decision-making, while allowing consideration of risk factors for PSSEH. Well-controlled studies are required to investigate further the relationship between BP and PSSEH.
HER2-positive advanced biliary tract cancer responds to second-line pyrotinib therapy: a case report
Authors: Liu Linger , Chen Yao , Zhu Xiaolian , Zhao Lisha , Chen Baisong
Published: December 2023

Biliary tract cancers are solid tumors with poor prognosis and over 70% of patients present in advanced stages. The efficacy of second-line treatment for patients who progressed on GC chemotherapy is limited. Median OS of these patients is less than 1 year with palliative treatment. Despite the success of anti-HER2 therapy in HER2-positive breast cancer, the targeted therapy of HER2 mutations in BTCs is still being explored. This case report is the first report suggesting a 15-month PFS and partial response of pyrotinib in HER2-positive BTC. We report a 64-year-old female with HER2-positive biliary tract cancer. She was diagnosed with AJCC clinical stage IV (cT3N1M1) intrahepatic biliary tract cancer and got PD after 3 cycles of systemic chemotherapy of gemcitabine plus cisplatin. Due to the HER2-positive signature, pyrotinib (400 mg daily in 21-day cycles), an oral irreversible pan-ErbB TKI was prescribed in September 2021, with her informed consent. The tumor shrank significantly after this treatment and imaging assessments conducted on 24 September 2022 showed PR. Until the writing of the case draft, the patient had achieved 15 months of PFS. The present case suggests that Pyrotinib might be a potential effective treatment for HER2-positive advanced BTC.