bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality characteristics of muffins prepared with different types of
rice flour
Authors: Chu Ji-Hye , Choi Jin-Hee , Go Eun-Seong , Choi Hae-Yeon
Published: September 2023

The quality characteristics of muffins with different types of rice flour, such
as soft flour (CON), soft rice flour (SRF), floury rice flour (FRF), and rice
flour (RF) were assessed by using Image J program, which includes their particle
size analysis, moisture content, pH, color, specific volume, baking loss rate,
texture. (D[4, 3]) is weighted mean diameter, which is directly obtained in
particle size measurements showed large values in the order of rice flour,
floury rice flour, soft rice flour, and soft flour. The moisture content was
high in the CON and SRF groups with small particle sizes. There was no
significant difference in pH, L and b value. The a value was significantly low
only in the RF group with large particle size. The smaller the particle size,
the higher the specific volume and baking loss rate. Image J showed that the
number of pores decreased when fewer smaller particles were the powder, but the
pores were larger. Among the rice flours, the SRF group, excluding the CON
group, scored high in all the acceptability elements. The results from this
study can be used as basic data that can contribute to research on various
rice-processed foods.
Roles of Kdm6a and Kdm6b in regulation of mammalian neural regeneration
Authors: Yang Shu-Guang , Wang Xue-Wei , Li Chang-Ping , Huang Tao , Qian Cheng , Li Qiao , Zhao Ling-Rui , Zhou Si-Yu , Ding Chen-Yun , Saijilafu  , Liu Chang-Mei , Zhou Feng-Quan
Published: September 2023

Epigenetic regulation of neuronal transcriptomic landscape is emerging to be a key coordinator of mammalian neural regeneration. Here we investigated roles of two histone 3 lysine 27 (H3K27) demethylases Kdm6a/b in controlling neuroprotection and axon regeneration. Deleting either Kdm6a or Kdm6b led to enhanced sensory axon regeneration in the PNS, whereas in the CNS only deleting Kdm6a in retinal ganglion cells (RGCs) significantly enhanced optic nerve regeneration. Moreover, both Kdm6a and Kdm6b functioned to regulate RGC survival but with different mechanisms. Mechanistically, Kdm6a regulates RGC regeneration via distinct pathway from that of Pten and co-deleting Kdm6a and Pten resulted in long distance optic nerve regeneration passing the optic chiasm. In addition, RNA-seq profiling revealed that Kdm6a deletion switched the RGC transcriptomics into a developmental-like state and suppressed several known repressors of neural regeneration. Klf4 was identified as a direct downstream target of Kdm6a-H3K27me3 signaling in both sensory neurons and RGCs to regulate axon regeneration. These findings not only revealed different roles of Kdm6a and Kdm6b in regulation of neural regeneration and their underlying mechanisms, but also identified Kdm6a- mediated histone demethylation signaling as a novel epigenetic target for supporting CNS neural regeneration.
Reentrant DNA shells tune polyphosphate condensate size
Authors: Chawla Ravi , Tom Jenna K. A. , Boyd Tumara , Grotjahn Danielle A. , Park Donghyun , Deniz Ashok A. , Racki Lisa R.
Published: September 2023

The ancient, inorganic biopolymer polyphosphate (polyP) occurs in all three domains of life and affects myriad cellular processes. An intriguing feature of polyP is its frequent proximity to chromatin, and in the case of many bacteria, its occurrence in the form of magnesium-enriched condensates embedded in the nucleoid, particularly in response to stress. The physical basis of the interaction between polyP and DNA, two fundamental anionic biopolymers, and the resulting effects on the organization of both the nucleoid and polyP condensates remain poorly understood. Given the essential role of magnesium ions in the coordination of polymeric phosphate species, we hypothesized that a minimal system of polyP, magnesium ions, and DNA (polyP-Mg2+-DNA) would capture key features of the interplay between the condensates and bacterial chromatin. We find that DNA can profoundly affect polyP-Mg2+coacervation even at concentrations several orders of magnitude lower than found in the cell. The DNA forms shells around polyP-Mg2+condensates and these shells show reentrant behavior, primarily forming in the concentration range close to polyP-Mg2+charge neutralization. This surface association tunes both condensate size and DNA morphology in a manner dependent on DNA properties, including length and concentration. Our work identifies three components that could form the basis of a central and tunable interaction hub that interfaces with cellular interactors. These studies will inform future efforts to understand the basis of polyP granule composition and consolidation, as well as the potential capacity of these mesoscale assemblies to remodel chromatin in response to diverse stressors at different length and time scales.
Biofluorescence reveals hidden patterns in chitons with implications to visual ecology
Authors: Grimaldi Guido G. , Guidi Raiane dos Santos , Jardim Jaime A. , Hirota Marina , Pessoa Daniel Marques Almeida , Horta Paulo Antunes
Published: September 2023

Biofluorescence is apparently widespread in the tree of life. Fluorescence has the potential to contribute to the totality of light leaving an organism’s surface and will therefore circumscribe how an individual could be detected and discriminated by their visual predators. Here, we: (i) documented the first record of biofluorescence on polyplacophorans, (ii) spectrally characterized the biofluorescence on shells of living chitons, (iii) measured the colour patch pattern variation, (iv) separated the colour of their shells into their reflectance and fluorescence components, and (v) combined these data with field measurements to calculate perceptual distance in chromatic and achromatic contrasts based on the visual system of their major visually guided predators. We found a red biofluorescence that enhances the brightness of chiton shells, along with a correlation showing that as individuals grow larger, the fluorescing surface area becomes smaller. Our visual models suggest that fluorescence decreases the achromatic contrast of chitons against their naturally fluorescent substrates for most visual predators, making them less noticeable to specific predators. Our results support the potential visual functionality of biofluorescence and open new hypotheses regarding its ecological roles to further investigations.
Safety Assessment of a Standardized Polyherbal Formulation (Glubloc™): Acute Toxicity Study and 28-Day Repeated Dose Toxicological Studies
Authors: Mayasa Vinyas , Raghuveer Pathuri , Chintamaneni Pavan Kumar , Gali Chaitanya Chakravarthi , Neerudu Uttam Kumar
Published: September 2023

The standardized extract ofMorus albaandMalus domestica Peelis widely recognized as a dietary supplement with potential benefits for blood sugar management, cholesterol reduction, and weight management. This study aimed to evaluate the general toxicity of the extract. Toxicity studies were conducted by OECD guidelines 425 and 407 and Schedule Y of the Drugs and Cosmetics Act, which mandates the use of two species for such studies. A single dose of GlublocTMat a concentration of 2000 mg/kg body weight was administered to Sprague Dawley rats and Albino mice, and no fatalities were reported, indicating good tolerability. Additionally, repeated oral administration of GlublocTMto rats and rabbits for a maximum duration of 28 days, at doses up to 414.16 mg/kg body weight per day in rats and 207.08 mg/kg body weight per day in rabbits, did not result in significant changes in medical assessments, ocular evaluations, weight gains, feeding behavior, or pathological findings compared to the control group. Overall, this study suggests that GlublocTMis well-tolerated without inducing any toxicity. The extract’s No-Observed-Adverse-Effect Level (NOAEL) is considered to be 414.16 mg/kg per day when administered repeatedly for 28 days in rats and 207.08 mg/kg in rabbits.
An effectiveC. elegansCRISPR training module for high school and undergraduate summer research experiences in molecular biology
Authors: Sandoval Carmen Herrera , Borchers Christopher , Aoki Scott Takeo
Published: September 2023

Engaging in research experiences as a high school or undergraduate student interested in science, technology, engineering, and mathematics (STEM) is pivotal for their academic and professional development. A structured teaching framework can help cultivate a student’s curiosity and passion for learning and research. In this study, an effective eight-week training program has been created that encompasses fundamental molecular biology principles and hands-on laboratory activities. This curriculum focuses on using clustered regularly interspaced short palindromic repeats (CRISPR) gene editing in theCaenorhabditis elegansmodel organism. Through pre- and post-program assessments, substantial enhancements in students’ molecular biology proficiency and enthusiasm for scientific exploration was observed. Overall, this diligently crafted training module that employsC. elegansas an educational tool to instruct inexperienced students has demonstrated its accessibility and ability to engage students in molecular biology and gene editing methodologies.
Impact of antibiotics and hospitalization on the nasopharyngeal microbiome in very preterm infants
Authors: Rajar Polona , Dhariwal Achal , Salvadori Gabriela , Åmdal Heidi Aarø , Berild Dag , Dahle Ulf R. , Fugelseth Drude , Greisen Gorm , Lausten-Thomsen Ulrik , Saugstad Ola Didrik , Petersen Fernanda Cristina , Haaland Kirsti
Published: September 2023

Rationale

Preterm infants are often exposed to antibiotics early in life. They are at increased risk for inflammation and infection due to immature immune system, weak mucosal barriers of the intestinal and respiratory tract and ineffective defense from non-pathogens of normal flora. Longitudinal research of respiratory microbiota of preterm infants is limited.

Objectives

Investigate the development of nasopharyngeal microbiota in preterm infants from birth until six months corrected age.

Methods

In our observational cohort study, we obtained 369 nasopharyngeal aspirates from 66 very preterm infants sampled at six time points spanning from birth until six months corrected age. Deep shotgun metagenomic sequencing was used to determine the microbiome composition.

Measurements and Main Results

Preterm infants were grouped according to postnatal antibiotic exposure (naïve; n=21, “Only Early antibiotics”; n=24 and “Other antibiotics”; n=21). Inter-individual variability, followed by postmenstrual age had the largest significant effect on the overall microbiome composition. We identified six microbial community types, determined by various abundances ofCutibacterium,Gemella, Serratia, Streptococcus and Staphylococcus. Antibiotic exposure resulted in significant, apparently transient diversity changes. The abundance ofSerratiaindicates that hospitalization can lead to microbiome scars lasting for at least six months after discharge.

Conclusions

Genera associated with respiratory health in non-premature populations were sparse. The respiratory microbiome of preterm infants is transiently affected by antibiotic exposure, while signatures of hospitalization may persist for at least six months after hospital discharge.
Most Hospitalized Patients with Significant Tricuspid Regurgitation Have Advanced Disease Preventing Transcatheter Tricuspid Valve Intervention
Authors: Dumitriu Carcoana Allison O. , Scoma Christopher B. , Maletz Sebastian N. , Malavet Jose A. , Crousillat Daniela R. , Matar Fadi A.
Published: September 2023

Background

More than moderate tricuspid regurgitation (TR) is associated with high mortality. Surgical tricuspid valve repair and replacements are rarely performed due to high operative mortality risk, mainly attributed to late presentation. Novel transcatheter tricuspid valve intervention (TTVI) devices are being developed as an alternative to surgery. The population of patients presenting to tertiary care centers who can benefit from TTVI has not been well defined. Our objective was to study the characteristics of these patients and to define the sub-population who may be candidates for TTVI.

Methods

We analyzed 12,677 consecutive 2D echocardiograms completed at our tertiary care center between March 2021 and March 2022 and identified 581 inpatients with more than moderate TR. Clinical and echocardiographic data were collected by individual chart review. The 2021 European Society of Cardiology (ESC) guidelines on the management of valvular disease are currently the only guidelines that include TTVI. We used these guidelines to retrospectively assign the 581 patients to medical therapy, surgery, or TTVI treatment.

Results

470 patients (80.9%) were assigned to medical therapy, 57 (9.8%) were assigned to TTVI, and 54 (9.3%) were assigned to tricuspid valve surgery. Of note, 76.2% (443/581) of patients were precluded from any intervention due to advanced disease or anatomic ineligibility, and only 4.6% (27/581) presented too early for intervention, being both asymptomatic and without RV dilatation.

Conclusion

Only 9.8 percent of patients presenting to a tertiary care center with significant TR would be hypothetical candidates for TTVI when these technologies are approved in the United States. Earlier identification and treatment of TR could increase the number of patients who may benefit from interventions including TTVI.

CLINICAL PERSPECTIVE

What is New?

Most patients presenting to a tertiary care center with significant TR are too advanced for any intervention and have high in-hospital and late mortality rates.

Tertiary care centers planning to offer TTVI should expect that, based on the current ESC guidelines and late presentation of TR, approximately 10% of patients with more than moderate TR will be TTVI candidates.

What are the clinical implications?

There is a need to improve care for patients with TR through earlier detection and referral for intervention.

Future clinical trials with longer follow up will be needed to assess TTVI devices in patients at earlier or even asymptomatic stages of TR when there may be a greater likelihood of improving survival.
Perioperative risk of non-cardiac surgery in patients with asymptomatic significant aortic stenosis: a 10-year retrospective study
Authors: Bak Minjung , Lee Seung-Hwa , Park Sung-Ji , Park Jungchan , Kim Jihoon , Kim Darae , Kim Eun Kyoung , Chang Sung-A , Lee Sang-Chol , Park Seung Woo
Published: September 2023

BACKGROUND

Aortic valve stenosis (AS) is a representative geriatric disease, and there is an anticipated rise in the number of patients requiring non-cardiac surgeries in patients with AS. However, there is still a lack of research on the primary predictors of non-cardiac perioperative complications in patients with asymptomatic significant AS.

METHOD AND RESULT

Among the cohort of non-cardiac surgeries under general anesthesia, with an intermediate-to-high risk of surgery from 2011 to 2019, at Samsung Medical Center, 221 patients were identified to have asymptomatic significant AS. First, to examine the impact of significant AS on perioperative adverse events, the occurrences of Major Adverse Cardiovascular Events (MACE) and Perioperative Adverse Cardiovascular Events (PACE) were compared between patients with asymptomatic significant AS and the control group. Second, to identify the factors influencing the perioperative adverse events in patients with asymptomatic significant AS, multivariable logistic regression model was used.

There was no significant difference between the three groups consisting of control group, moderate asymptomatic AS group, and severe asymptomatic AS group in the event rate of MACE (p value 0.971) and PACE (p value 0.185). Cardiac damage stage was significant risk factor of MACE (OR 9.241, 95% CI: 1.314 - 64.976, p-value = 0.025) and PACE (OR 2.199, 95% CI: 1.055 - 4.584, p-value = 0.036).

CONCLUSION

There was no significant difference in major post-operative cardiovascular events between patients with asymptomatic significant AS and the control group. Advanced cardiac damage stage in significant AS is a key factor in perioperative risk of non-cardiac surgery.

CLINICAL PERSPECTIVE

What Is New?

Advanced cardiac damage is a major risk factor for perioperative complications in non-cardiac surgeries of patients with asymptomatic significant AS.

What Are the Clinical Implications?

Patients with asymptomatic significant AS showed no significant difference in perioperative complications compared to the control group, but caution is needed in those with advanced cardiac damage, as they are more likely to experience adverse events.
Fully addressable, designer superstructures assembled from a single modular DNA origami
Authors: Weck Johann M. , Heuer-Jungemann Amelie
Published: September 2023

Intricate self-organization is essential in many biological processes, underpinning vital functions and interactions. In an effort to mimic such processes, synthetic biology aims to engineer dynamic structures with controllable functions using nanotechnological tools. A key requirement of engineered building blocks is the ability to assemble and disassemble hierarchically with precision. Using the DNA origami technique, we here present the moDON, a modular DNA origami nanostructure, which is capable of assembling into almost 20 000 diverse monomers, forming complex and controlled superstructures in three dimensions. While shape and addressability of DNA origami are nearly arbitrary, its overall size is limited by the scaffold size. Previous methods of extending the size of DNA origami (e.g. hierarchical assembly, modified scaffolds, etc.), either led to loss over control of shape and addressability beyond monomers or to proportionally increased cost and design effort. With the moDON we were able to overcome both issues. The modular design combines xy- and z-plane assembly methods, enabling the construction of finite and periodic structures beyond 1 GDa. We demonstrate xy-z orthogonality, by enabling controlled selective or parallel assembly and disassembly via distinct orthogonal triggers. The kinetic profile of assembly and disassembly aligns with biological time scales, paving the way for applications in dynamic nanomachinery and advanced biomaterials. Finally, we showcase the conjugation of gold nanoparticles to specific positions within superstructures, underscoring the efficacy of this approach for creating intricate and orthogonal nanoscale architectures with preserved site-specific addressability. The moDON thus offers an efficient, cost-effective solution for constructing large, precisely organized, and fully addressable structures with vast potential in synthetic cellular systems design.
Artificial neural networks for model identification and parameter estimation in computational cognitive models
Authors: Rmus Milena , Pan Ti-Fen , Xia Liyu , Collins Anne G. E.
Published: September 2023

1

Computational cognitive models have been used extensively to formalize cognitive processes. Model parameters offer a simple way to quantify individual differences in how humans process information. Similarly, model comparison allows researchers to identify which theories, embedded in different models, provide the best accounts of the data. Cognitive modeling uses statistical tools to quantitatively relate models to data that often rely on computing/estimating the likelihood of the data under the model. However, this likelihood is computationally intractable for a substantial number of models. These relevant models may embody reasonable theories of cognition, but are often under-explored due to the limited range of tools available to relate them to data. We contribute to filling this gap in a simple way using artificial neural networks (ANNs) to map data directly onto model identity and parameters, bypassing the likelihood estimation. We test our instantiation of an ANN as a cognitive model fitting tool on classes of cognitive models with strong inter-trial dependencies (such as reinforcement learning models), which offer unique challenges to most methods. We show that we can adequately perform both parameter estimation and model identification using our ANN approach, including for models that cannot be fit using traditional likelihood-based methods. We further discuss our work in the context of the ongoing research leveraging simulation-based approaches to parameter estimation and model identification, and how these approaches broaden the class of cognitive models researchers can quantitatively investigate.

2

Author Summary

Computational cognitive models occupy an important position in cognitive science research, as they offer a simple way of quantifying cognitive processes (such as how fast someone learns, or how noisy they are in choice selection), and testing which cognitive theories offer a better explanation of the behavior. To relate cognitive models to the behavioral data, researchers rely on statistical tools that require estimating the likelihood of observed data under the assumptions of the cognitive model. This is, however, not possible to do for all models as some models present significant challenges to likelihood computation. In this work, we use artificial neural networks (ANNs) to bypass likelihood computation and approximation altogether, and demonstrate the success of this approach applied to model parameter estimation and model comparison. The proposed method is a contribution to ongoing development of modeling tools which will enable cognitive researchers to test a broader range of theories of cognition.
Ellagic acid ameliorates atherosclerosis by targeting the epidermal growth factor receptor
Authors: Huang Ye-Wei , Wang Li-Tian , Yin Huai-Liu , Hu Dan-Dan , Sheng Jun , Wang Xuan-Jun
Published: September 2023

BACKGROUND

High levels of plasma low-density lipoprotein (LDL) are a key risk factor for atherosclerosis. Low-density lipoprotein receptor (LDLR) mediates the degradation of plasma LDL. Therefore, it may be possible to prevent and treat atherosclerosis by increasing the levels of LDLR. The natural polyphenolic compound ellagic acid (EA) has various biological activities. In mice, EA alleviated the progression of atherosclerosis; however, the underlying mechanism remains unclear.

METHODS

Molecular interaction, cell, and animal experiments were used to explore the role and mechanism of EA in improving atherosclerosis.

RESULTS

EA binds to the extracellular domain of the epidermal growth factor receptor (EGFR), thus activating the EGFR-extracellular signal-regulated kinase (EGFR-ERK) signaling pathway, stabilizing LDLR mRNA, and promoting the expression of LDLR protein. The development of EA-loaded human serum albumin nanoparticles enabled intravenous administration in animal experiments.

CONCLUSIONS

The research verified the in vivo effects of EA on the EGFR-ERK signaling pathway, LDLR levels, and atherosclerosis. EA may assist in the prevention and treatment of atherosclerosis.
CRISPR-Cas9 Engineered Extracellular Vesicles for the Treatment of Dominant Progressive Hearing Loss
Authors: Pan Xiaoshu , Huang Peixin , Ali Samantha S. , Renslo Bryan , Hutchinson Tarun E , Erwin Nina , Greenberg Zachary , Ding Zuo , Li Yanjun , Warnecke Athanasia , Fernandez Natalia E. , Staecker Hinrich , He Mei
Published: September 2023

Clinical translation of gene therapy has been challenging, due to limitations in current delivery vehicles such as traditional viral vectors. Herein, we report the use of gRNA:Cas9 ribonucleoprotein (RNP) complexes engineered extracellular vesicles (EVs) forin vivogene therapy. By leveraging a novel high-throughput microfluidic droplet-based electroporation system (μDES), we achieved 10-fold enhancement of loading efficiency and more than 1000-fold increase in processing throughput on loading RNP complexes into EVs (RNP-EVs), compared with conventional bulk electroporation. The flow-through droplets serve as enormous bioreactors for offering millisecond pulsed, low-voltage electroporation in a continuous-flow and scalable manner, which minimizes the Joule heating influence and surface alteration to retain natural EV stability and integrity. In the Shaker-1 mouse model of dominant progressive hearing loss, we demonstrated the effective delivery of RNP-EVs into inner ear hair cells, with a clear reduction ofMyo7ash1mRNA expression compared to RNP-loaded lipid-like nanoparticles (RNP-LNPs), leading to significant hearing recovery measured by auditory brainstem responses (ABR).

One sentence summary

The scalable microfluidic electroporation system enables the loading of gRNA:Cas9 ribonucleoprotein (RNP) complexes into extracellular vesicles, which leads to clinical translation potential employed in hearing disease gene therapy.
Low-latency extracellular spike assignment for high-density electrodes at single-neuron resolution
Authors: Lai Chongxi , Kim Dohoung , Lustig Brian , Tanaka Shinsuke , Barbarits Brian , Narayan Lakshmi , Colonell Jennifer , Paulsen Ole , Lee Albert K. , Harris Timothy D.
Published: September 2023

Real-time neural signal processing is essential for brain-machine interfaces and closed-loop neuronal perturbations. However, most existing applications sacrifice cell-specific identity and temporal spiking information for speed. We developed a hybrid hardware-software system that utilizes a Field Programmable Gate Array (FPGA) chip to acquire and process data in parallel, enabling individual spikes from many simultaneously recorded neurons to be assigned single-neuron identities with 1-millisecond latency. The FPGA assigns labels, validated with ground-truth data, by comparing multichannel spike waveforms from tetrode or silicon probe recordings to a spike-sorted model generated offline in software. This platform allowed us to rapidly inactivate a region in vivo based on spikes from an upstream neuron before these spikes could excite the downstream region. Furthermore, we could decode animal location within 3 ms using data from a population of individual hippocampal neurons. These results demonstrate our system’s suitability for a broad spectrum of research and clinical applications.
Neurodegeneration is strongly linked to heart failure severity and outcomes: framing the cardiocerebral syndrome
Authors: Wurm Raphael , Prausmüller Suriya , Ponleitner Markus , Spinka Georg , Weidenhammer Annika , Arfsten Henrike , Heitzinger Gregor , Panagiotides Noel Gilian , Bartko Philipp , Goliasch Georg , Stögmann Elisabeth , Hengstenberg Christian , Hülsmann Martin , Pavo Noemi
Published: September 2023

Background and Objectives

Cognitive impairment is prevalent in patients with heart failure with reduced ejection fraction (HFrEF), affecting self-care and outcomes. Novel blood-based biomarkers have emerged as potential diagnostic tools for neurodegeneration. This study aimed to assess neurodegeneration in HFrEF by measuring neurofilament light chain (NfL), total tau (t-tau), amyloid-beta 42 (Aβ42), and 40 (Aβ40) in a large, well-characterised cohort.

Methods

The study included 470 HFrEF patients from a biobank-linked prospective registry at the Medical University of Vienna. High-sensitivity single-molecule assays were used for measurement. Unplanned hospitalisations and all-cause death were recorded as outcome parameters.

Results

All markers, but not the Aβ42/Aβ40 ratio, correlated with heart failure (HF) severity, i.e. NTproBNP and NYHA class, comorbidity burden and were significantly associated with all-cause death and HF-hospitalisations [crude HR for 1-log unit increase (95%CI): 4.44 (3.02-6.53), 5.04 (2.97-8-58), 3.90 (2.27-6.72) and 5.14 (2.84-9.32) for all-cause death and 2.48 (1.60-3.85), 3.44 (1.95-6.04), 3.13 (1.84-5.34) and 3.48 (1.93-6.27) for HHF, p<0.001 for all]. These markers remained significant after adjustment in multivariate models including NT-proBNP. NfL and t-tau showed the highest prognostic ability in the receiver operating characteristic analysis [AUC: 0.72, 0.68, 0.66, 0.67 for NfL, t-tau, Aβ40 and Aβ42, respectively]. The performance of NfL was comparable to that of NT-proBNP [C-index: 0.70 vs 0.72, p=0.225].

Conclusions

Neurodegeneration is directly interwoven with the progression of HF. Biomarkers, particularly NfL, may help identify patients profiting from detailed neurological workups. Further research is necessary to test if early diagnosis or optimised HFrEF treatment can preserve cognitive function.
Tobacco Dependency in the United Kingdom: Prevalence, Risk Factors, Interventions, Disparities, and Policy Implications
Authors: Weerakoon Tharumini
Published: September 2023

Tobacco dependency remains a persistent global public health challenge, with significant implications for morbidity, mortality, and healthcare costs. This systematic review presents a comprehensive analysis of tobacco dependency studies conducted in the United Kingdom (UK). The objective is to distill existing research to inform evidence-based interventions and policies targeting this pressing issue.

The primary purpose of this systematic review is to provide an up-to-date synthesis of the current state of tobacco dependency in the UK. By examining a wide range of studies, we aim to identify trends, risk factors, and effective interventions, ultimately contributing to the development of targeted strategies for reducing tobacco use in the UK population.

A rigorous systematic search across various academic databases yielded a substantial body of evidence encompassing diverse study designs, including epidemiological surveys, qualitative investigations, and intervention trials. Studies meeting predefined inclusion criteria were systematically reviewed and assessed for quality. Key themes explored include the prevalence of tobacco dependency, associated risk factors, intervention effectiveness, and disparities across demographic groups.

Our review highlights several critical findings:

The prevalence of tobacco dependency in the UK has declined over the past decade, but challenges persist, particularly among vulnerable populations.

Multiple risk factors, including socioeconomic status, mental health conditions, and peer influences, contribute to tobacco dependency in the UK.

Evidence supports the effectiveness of various interventions, including smoking cessation programs, taxation policies, and public awareness campaigns.

Disparities in tobacco dependency exist along demographic lines, necessitating targeted strategies to address these inequalities.

Understanding the complex landscape of tobacco dependency in the UK is imperative for informing public health policies and interventions. This systematic review underscores the need for continued efforts to reduce tobacco use, particularly among disadvantaged groups. The identified risk factors and effective interventions provide valuable insights for designing evidence-based strategies to combat tobacco dependency and its associated health and economic burdens. Addressing these challenges is essential for improving the overall well-being and health equity of the UK population.
Transcriptomic signatures of Aβ- and tau-induced neuronal dysfunction reveal inflammatory processes at the core of Alzheimer’s disease pathophysiology
Authors: Sanchez-Rodriguez Lazaro M. , Khan Ahmed F. , Adewale Quadri , Bezgin Gleb , Therriault Joseph , Fernandez-Arias Jaime , Servaes Stijn , Rahmouni Nesrine , Tissot Cécile , Stevenson Jenna , Jiang Hongxiu , Chai Xiaoqian , Carbonell Felix , Rosa-Neto Pedro , Iturria-Medina Yasser
Published: September 2023

Molecular mechanisms enabling pathology-induced neuronal dysfunction in Alzheimer’s disease (AD) remain elusive. Here, we use mechanistic computational models to infer the combined influence of PET-measured Aβ and tau burdens on fMRI-derived neuronal activity and to subsequently identify the transcriptomic spatial correlates of AD pathophysiology. Our results reveal overrepresented genes and biological processes that participate in synaptic degeneration and interact with Aβ and tau deposits. Furthermore, we confirmed the central role of the immune system and neuroinflammatory pathways within AD pathogenesis; microglia were significantly enriched in the gene set associated with Aβ and tau synergistic influences on neuronal activity. Lastly, our computational approach unveiled drug candidates with the potential to halt or reduce the observed pathological effects on neuronal activity, including existing medication for cancer, immune disorders, and cardiovascular diseases, many currently under clinical evaluation in AD. Overall, these findings support the notion that the AD brain experiences functional changes intricately associated with a diverse spectrum of molecular processes.
Loss of G9a does not phenocopy the requirement for Prdm12 in the development of the nociceptive neuron lineage
Authors: Tsimpos Panagiotis , Desiderio Simon , Cabochette Pauline , Kricha Sadia , Bellefroid Eric J.
Published: September 2023

Prdm12 is an epigenetic regulator expressed in developing and mature nociceptive neurons, playing a key role in their specification during neurogenesis and modulating pain sensation at adulthood.In vitrostudies suggested that Prdm12 recruits the methyltransferase G9a through its zinc finger domains to regulate target gene expression, but how Prdm12 interacts with G9a and whether G9a plays a role in Prdm12’s functional properties in sensory ganglia remain unknown. Here we report that the SET domain of G9a is necessary and sufficient for the interaction with Prdm12. We show that Prdm12 is co-expressed with G9a in dorsal root ganglia during early murine development. To address the role of G9a in somatosensory neurogenesis and test the hypothesis that it may function as a mediator of Prdm12’s function during somatosensory neurogenesis, we conditionally inactivated it in neural crest using a Wnt1-Cre transgenic mouse line. We found that G9a ablation in neural crest does not lead to dorsal root ganglia hypoplasia due to the loss of somatic nociceptive neurons nor to the ectopic expression of the visceral determinant Phox2b as observed uponPrdm12ablation. Together, our results confirm Prdm12’s ability to interact with G9a and reveal that this interaction is however not instrumental for its developmental function during nociceptive neuron development.
The internal metabolic state controls behavior inHydrathrough an interplay of enteric and central nervous system-like neuron populations
Authors: Giez Christoph , Noack Christopher , Sakib Ehsan , Bosch Thomas
Published: September 2023

Hunger and satiety can have an influence on decision making, sensory processing, and motor behavior by altering the internal state of the brain. This process necessitates the integration of peripheral sensory stimuli into the central nervous system. Interestingly, even organisms without a brain, such as the Cnidaria, exhibit feeding dependent behavioral changes. The underlying mechanisms, however, remain unclear. In this study, we demonstrate that neuronal activity in two distinct neuronal populations, the ectodermal N3 neurons and the endodermal N4 neurons inHydra, an ancestral metazoan animal with a diffuse nerve net spread throughout the body with no signs of centralization, are responsible for feeding dependent behavioral changes. Specifically, endodermal N4 neurons are essential for food intake and digestive functions, similar to the enteric nervous system, while the N3 population influences and inhibits other motor related behaviors, comparable to the central nervous system. This fascinating observation provides a new insight into the evolution and the complexity of a simple non-centralized nervous system.
Cardiorespiratory fitness is associated with neuroelectric activity complexity in children with overweight or obesity
Authors: Minguillon Jesus , Perez-Valero Eduardo , Lopez-Gordo Miguel A. , Esteban-Cornejo Irene , Ortega Francisco B. , Mora-Gonzalez Jose
Published: September 2023

Cardiorespiratory fitness is one of the most important markers of health. Several studies have demonstrated the relationship between cardiorespiratory fitness and brain functioning in healthy children. Some of these works suggested that cardiorespiratory fitness may have a protective role on the executive function, which represents a set of cognitive mechanisms used to control and coordinate other cognitive abilities. This is particularly relevant in children with overweight or obesity. In these studies, neuroelectric activity is recorded using medical imaging techniques or electroencephalography (EEG). Among the EEG studies, analyses based on the P3 event related potential stand out. However, complementary analyses are necessary to understand the neural mechanisms underlying the associations between cardiorespiratory fitness and brain functioning. EEG complexity, a useful feature that measures the regularity of neuroelectric activity, has been previously associated with cardiorespiratory fitness in adolescents. In this work, we evaluate this association in a group of 87 Caucasian children with overweight/obesity. Our results reveal that the children with higher cardiorespiratory fitness present less EEG complexity while performing a cognitive task that challenges the executive function. In addition, they suggest that the line length, the metric that we used to estimate EEG complexity, performs equally well as those metrics based on the P3 and better than other complexity metrics like sample entropy, as an indicator of cardiorespiratory fitness. Finally, the line length has advantages over the P3: more consistency across EEG regions and cognitive loads, lower experimental complexity, lower computational cost, and higher automatization capability.
In-vivo characterization of magnetic inclusions in the subcortex from non-exponential transverse relaxation decay
Authors: Oliveira Rita , Raynaud Quentin , Jelescu Ileana , Kiselev Valerij G. , Kirilina Evgeniya , Lutti Antoine
Published: September 2023

According to theoretical studies, the MRI signal decay due to transverse relaxation, in brain tissue with magnetic inclusions (e.g. blood vessels, myelin, iron-rich cells), exhibits a transition from a Gaussian behaviour at short echo times to exponential at long echo times. Combined, the Gaussian and exponential decay parameters carry information about the inclusions (e.g., size, volume fraction) and provide a unique insight into brain tissue microstructure. However, gradient echo decays obtained experimentally typically only capture the long-time exponential behaviour. Here, we provide experimental evidence of non-exponential transverse relaxation signal decay at short times in human subcortical grey matter, from MRI data acquired in vivo at 3T. The detection of the non-exponential behaviour of the signal decay allows the subsequent characterization of the magnetic inclusions in the subcortex.

The gradient-echo data was collected with short inter-echo spacings, a minimal echo time of 1.25 ms and novel acquisition strategies tailored to mitigate the effect of motion and cardiac pulsation. The data was fitted using both a standard exponential model and non-exponential theoretical models describing the impact of magnetic inclusions on the MRI signal. The non-exponential models provided superior fits to the data, indicative of a better representation of the observed signal. The strongest deviations from exponential behaviour were detected in the substantia nigra and globus pallidus. Numerical simulations of the signal decay, conducted from histological maps of iron concentration in the substantia nigra, closely replicated the experimental data – highlighting that non-heme iron can be at the source of the non-exponential signal decay.

To investigate the potential of the non-exponential signal decay as a tool to characterize brain microstructure, we attempted to estimate the properties of the inclusions at the source of this decay behaviour using two available analytical models of transverse relaxation. Under the assumption of the static dephasing regime, the magnetic susceptibility and volume fractions of the inclusions was estimated to range from 1.8 to 4 ppm and from 0.02 to 0.04 respectively. Alternatively, under the assumption of the diffusion narrowing regime, the typical inclusion size was estimated to be ∼2.4μm. Both simulations and experimental data point towards an intermediate regime with a non-negligible effect of water diffusion to signal decay. Non-exponential transverse relaxation decay provides new means to characterize the spatial distribution of magnetic material within subcortical grey matter tissue with increased specificity, with potential applications to Parkinson’s disease and other pathologies.
Erdr1 orchestrates macrophage polarization and determines cell fate via dynamic interplay with YAP1 and Mid1
Authors: Wang Yuhang
Published: September 2023

Erythroid differentiation regulator 1 (Erdr1) is a stress-induced, widely distributed, extremely conserved secreted factor found in both humans and mice. Erdr1 is highly linked with the Hippo-YAP1 signaling. Initially identified as an inducer of hemoglobin synthesis, it has emerged as a multifunctional protein, especially in immune cells. Although Erdr1 has been implicated in T cells and NK cell function, its role in macrophage remains unclear. This study aims to explore the function and mechanism of Erdr1 in IL-1β production in macrophages. Data manifest Erdr1 could play an inhibition role in IL-1β production, which also has been reported by previous research. What significance is we discovered Erdr1 can promote IL-1β production which is associated with Erdr1 dose and cell density. We observed that Erdr1 was inhibited in pro-inflammatory (M1) macrophages but was upregulated in anti-inflammatory (M2) macrophages compared to naive macrophages. We hypothesized that Erdr1 dual drives and modulates IL-1β production by binding with distinct adaptors via concentration change. Mechanistically, we demonstrated that Erdr1 dual regulates IL-1β production by dynamic interaction with YAP1 and Mid1 by distinct domains. Erdr1-YAP1 interplay mediates macrophage M2 polarization by promoting an anti-inflammatory response, enhancing catabolic metabolism, and leading to sterile cell death. Whereas, Erdr1-Mid1 interplay mediates macrophage M1 polarization by initiating a pro-inflammatory response, facilitating anabolic metabolism, and causing inflammatory cell death. This study highlights Erdr1 orchestrates macrophage polarization and determines cell date by regulating YAP1 through non-classical Hippo pathway.
Measuring and Reducing Racial Bias in a Pediatric Urinary Tract Infection Model
Authors: Anderson Joshua W. , Shaikh Nader , Visweswaran Shyam
Published: September 2023

Clinical predictive models that include race as a predictor have the potential to exacerbate disparities in healthcare. Such models can be respecified to exclude race or optimized to reduce racial bias. We investigated the impact of such respecifications in a predictive model – UTICalc – which was designed to reduce catheterizations in young children with suspected urinary tract infections. To reduce racial bias, race was removed from the UTICalc logistic regression model and replaced with two new features. We compared the two versions of UTICalc using fairness and predictive performance metrics to understand the effects on racial bias. In addition, we derived three new models for UTICalc to specifically improve racial fairness. Our results show that, as predicted by previously described impossibility results, fairness cannot be simultaneously improved on all fairness metrics, and model respecification may improve racial fairness but decrease overall predictive performance.
Uptake, safety, and effectiveness of inactivated influenza vaccine in patients with inflammatory bowel disease: a nationwide study in the UK using data from the Clinical Practice Research Datalink
Authors: Nakafero Georgina , Grainge Matthew J. , Card Tim , Mallen Christian D. , Nguyen Van-Tam Jonathan S. , Abhishek Abhishek
Published: September 2023

Objective

We investigated UK wide inactivated influenza vaccine (IIV) uptake in adults with inflammatory bowel disease (IBD), the association between vaccination against influenza and IBD flare, and the effectiveness of IIV in preventing morbidity and mortality.

Design

Data for adults with IBD prior to 1stSeptember 2018 were extracted from the Clinical Practice Research Datalink (CPRD) Gold, a database of electronic health records originated during routine care of patients in the UK. It is linked to hospitalization and mortality records. We calculated the proportion of patients vaccinated against seasonal influenza in the 2018-2019 influenza cycle. To investigate vaccine effectiveness, we calculated propensity score (PS) for vaccination and undertook Cox proportional hazard regression with inverse-probability treatment weighting on PS. We employed self-controlled case series (SCCS) to investigate the association between vaccination and IBD flare.

Results

Data for 13,631 IBD patients (50.4% male, mean age 52.9 years) were included. Fifty percent were vaccinated during the influenza cycle while 32.1% were vaccinated before influenza virus circulated in the community. Vaccination was associated with a non-significant reduction in hospitalisation for pneumonia (aHR (95%CI) 0.52 (0.20-1.37), including in the influenza active period (aHR (95%CI) 0.48 (0.18-1.27)). Administration of the influenza vaccine was not associated with IBD flare.

Conclusion

The uptake of influenza vaccine is low in IBD patients and the majority are not vaccinated before influenza virus circulates in the community. Vaccination with the IIV is not associated with IBD flare. These findings add to the evidence to promote vaccination in patients with IBD.

Key messages

What is already known on the topic

Inactivated influenza vaccine is recommended in people with IBD treated with immune suppressing drugs.

Concerns about influenza vaccine causing IBD flare and lack of data on the effectiveness of influenza vaccine in people with IBD are barriers to seasonal influenza vaccination in this population.

What this study adds

The uptake of seasonal influenza vaccination is low in IBD patients.

Seasonal influenza vaccination is not associated with IBD flare and is more likely to prevent serious complications of influenza in this population.

How this study might affect research, practice, or policy

This study provides new data on the uptake, effectiveness, and safety of influenza vaccine in people with IBD and adds to the accumulating evidence to promote vaccination in this population.