bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mendelian analysis of the causality between inflammatory cytokines and digestive tract cancers
Authors: Ren Xing , Hu Rong , Zhang Hui
Published: October 2024

Purpose

In this study, we performed a two-sample Mendelian randomization (MR) analysis to assess the causality between inflammatory cytokines and the risk of digestive tract cancers (DTCs). Furthermore, we conducted a molecular docking study to predict the therapeutic mechanisms of traditional Chinese medicine (TCM) compounds in the treatment of DTCs.

Methods

In our MR analysis, genetic variations associated with eight types of DTCs were utilized, which were sourced from a large publicly available genome-wide association study dataset (7929 cases and 1 742 407 controls of European ancestry) and inflammatory cytokines data from a genome-wide association study summary of 8293 European participants. Inverse-variance weighted method, MR-Egger, and weighted median were performed to analyze and strengthen the final results. We investigated the effects of 41 inflammatory molecules on 8 types of DTCs. Subsequently, the effect of DTCs on positive inflammatory factors was analyzed by means of inverse MR. Molecular docking was exploited to predict therapeutic targets with TCM compounds.

Results

Interleukin-7, interleukin-16, macrophage colony-stimulating factor, monokine induced by interferon-gamma, and vascular endothelial growth factor may be significantly associated with various types of DTCs. Five TCM compounds (baicalin, berberine, curcumin, emodin, and salidroside) demonstrated better binding energies to both interleukin-7 and vascular endothelial growth factor than carboplatin.

Conclusion

This study provides strong evidence to support the potential causality of some inflammatory cytokines on DTCs and indicates the potential molecular mechanism of TCM compounds in the treatment of DTCs.

Key message What is already known on this topic  The increasing evidence indicates that inflammatory cytokines are implicated in the pathogenesis of digestive tract cancers (DTCs). Nevertheless, the causal relationship between inflammatory cytokines and DTCs remains indistinct. Additionally, certain traditional Chinese medicine compounds have been demonstrated to treat DTCs by influencing inflammatory factors, yet their underlying potential mechanisms remain ambiguous. What this study adds  In this study, Mendelian randomization analysis was performed for the first time regarding the causality between human inflammatory cytokines and eight types of DTCs, which revealed that inflammatory factors may play different roles in different types of DTCs. Moreover, molecular docking of key inflammatory factors was implemented, indicating the targets for drug actions. How this study might affect research, practice, or policy  This research has the potential to reveal the causality between 41 inflammatory factors and 8 DTCs, offering novel perspectives for the prevention and management strategies of DTCs. Additionally, it indicates the targets for the actions of traditional Chinese medicine on the key inflammatory factors of these cancers.
Emotional Support and Financial Distress
Authors: Ke Da
Published: October 2024

This paper is the first to explore emotional support as an important determinant of household financial outcomes. Using microdata from the United States and Australia, I document that individuals who feel emotionally supported are less likely to experience financial distress. This relationship is not confounded by nonemotional aspects of social support and is confirmed by between-siblings and within-individual analyses. Further investigation suggests emotional support helps to overcome psychological barriers that impede individuals from taking precautions against adverse shocks. Moreover, when such shocks occur, those with strong emotional support can better cope with the adversity as emotional support boosts their confidence. (JEL D14, D91, G41, G51, Z13)
Cost-effectiveness of allergen immunotherapy
Authors: Rodríguez-Otero Natalia , Ramírez-Mateo Elena , Plana Maria Nieves , Heffler Enrico , Antolín-Amérigo Darío
Published: October 2024

Purpose of review

Allergic rhinitis is a relevant and global health problem affecting up to 5–50% of the general population and its prevalence is increasing due to climate change and pollution among other factors and counts among the 10 most frequent reasons for medical consultation, generating an important economic impact. Allergen immunotherapy (AIT) is the only allergy-disease-modifying treatment and there is plenty of evidence of its effectiveness with regards subcutaneous and oral routes of AIT.

This narrative review article examines published literature in the last 24 months regarding the pharmacoeconomics of AIT versus standard of care treatment (SOC) for the treatment of allergic rhinitis and asthma.

Recent findings

Farraia et al. assessed in 2022 subcutaneous immunotherapy (SCIT, _438/$500.28) and sublingual immunotherapy (SLIT) (_1021/$1116.19) plus symptomatic treatment versus SOC treatment in children with HDM-driven allergic asthma, measuring QALYs, decrease of medication, decrease of exacerbations and symptoms. They used the cost-effective threshold: _18 482.80 ($21 110.14), finding that AIT is cost-effective.

Also, SCIT and SLIT plus symptomatic treatment was assessed versus SOC treatment in children with grass pollen allergic rhinitis. The authors concluded that SCIT (_933/$1065.67) and SLIT (_1408/ $1608.22) seem cost-effective, particularly SCIT.

Allergen immunotherapy is cost-effective in the management of allergic rhinitis and asthma as compared with SOC alone. As most studies consider only during-treatment costs and no long-term benefits or preventive effects are being assessed, the real cost-effectiveness of allergen immunotherapy could be even higher.
Dual-Plane Treatment With Highly Concentrated Hybrid Cooperative Complexes of Hyaluronans for Facial Atrophic Acne Scars
Authors: Sparavigna Adele , Grimolizzi Franco , Cigni Clara , Lualdi Roberto , Bellia Gilberto
Published: October 2024

BACKGROUND

Managing patients with acne scars remains an important challenge, as scarring negatively affects psychosocial wellbeing. Hyaluronic acid (HA) cross-linked fillers have demonstrated good efficacy and tolerability for the correction of acne scars but are limited by their reduced biological activity and low concentrations.

OBJECTIVE

This study investigated the efficacy and safety on scars of a high-concentration (4.5%) HA-based filler with hybrid cooperative complexes (HCC) of high-molecular-weight and low-molecular-weight HA.

METHODS

Participants received treatment twice; the first was provided at baseline (T0) and the second after 4 weeks (T1). Data were collected at T1 and after 4 months (T2) by photographs and instrumental evaluation of the skin.

RESULTS

The study population included 28 patients. Improvements in the mean Goodman and Baron grade were significant across time points T0 and T1 (12% improvement; p = .0002) and T0 and T2 (31% improvement; p < .0001). Instrumental evaluation of the skin surface demonstrated a 20% reduction in the average deepness of acne scars after 4 months (p < .0001). No serious adverse events were reported during the study procedure.

CONCLUSION

Highly concentrated (4.5%) HCC appears to be an effective option for the correction of facial acne scars.
Evaluation of the Danish Colorectal Cancer Screening Program Among People With Cystic Fibrosis
Authors: Exsteen Banoo B. , Katzenstein Terese L. , Faurholt-Jepsen Daniel , Bjerregaard Niels C. , Bader-Larsen Karlen , Jensen-Fangel Soeren , Mynster Tommie
Published: October 2024

Goals:

We aimed to evaluate the Danish CRC screening program, estimate colonic neoplasia's prevalence, and assess the utilized BP regimens.

Background:

People with cystic fibrosis (pwCF) have an increased risk of precancerous polyps and colorectal cancer (CRC), with occurrence at an earlier age compared with the general population. Consequently, colonoscopy screening is recommended. PwCF requires specific bowel preparation (BP) regimens to ensure an adequate colonoscopy.

Study:

We conducted a national retrospective cohort study, which included all pwCF eligible for colonoscopy according to international recommendations in 26 months.

Results:

Among 119 eligible pwCF, 58 completed colonoscopies during the screening period. The screening was omitted in 25% of pwCF. Among the pwCF undergoing colonoscopy screening, precancerous polyps were found in 24% and none with CRC. One patient developed CRC before being offered screening. Risk factors for neoplasia were old age and male sex. The quality of BP was high, even though most pwCF received standard BP. The best quality was found in nonorgan transplanted, pwCF who received modulator treatment and those with no laxatives use.

Conclusions:

We detected a high adherence to CRC screening, but also a substantial proportion of pwCF who were not informed about screening recommendations, calling for greater awareness among clinicians. Although lower than previously described, our study revealed high numbers of precancerous polyps and CRC compared with the general population, underlining the need for screening. BP quality remained high, despite frequent use of standard regimens, implicating the need for more individualized regimens before undergoing colonoscopy.
Postoperative management following endoscopic skull base surgery
Authors: Vozel Domen , Urbančič Jure
Published: October 2024

Purpose of review

The purpose of this opinion is to review current evidence regarding postoperative management following endoscopic skull base surgery.

Recent findings

Postoperative management encompasses consideration of level of care, laboratory tests, analgetic and antiemetic therapy, antibiotic, antithrombotic and antiepileptic prophylaxis, pharmacological and nonpharmacological cerebrospinal fluid (CSF) pressure reduction measures, including CSF diversion, activity restrictions, nasal packing removal, nasal debridement and toilet, nasal glucocorticoid administration, positive pressure ventilation, imaging, CSF leak diagnosis, and future perspectives.

Although significant effort has been put into research of postoperative measures after endoscopic skull-base surgery, there is a heterogeneity of practices and deficit of high-level studies, which would enable highly powered systematic reviews and meta-analyses.
REACTIVE ARTHRITIS: A CASE REPORT AT THE MOHAMMED V MILITARY TRAINING HOSPITAL IN RABAT
Authors: Laatiris laatiris Hamid , Zniber Nabil , El Mostafa el mostafa Benaissa , Benlahlou benlahlou Yassine , Chadli chadli Mariama
Published: October 2024

Reactive arthritis (RA) is a type of joint inflammation that usually occurs after a genitourinary or digestive infection, without the presence of germs in the joint itself. It often presents as asymmetric arthritis, joint pain, swelling, deformities in fingers or toes, and various skin or mucosal symptoms. The diagnosis is mainly based on clinical signs and is frequently associated with spondyloarthropathies, with severe cases often linked to the presence of the HLA-B27 gene.We present the case of a 23-year-old patient admitted to the Mohammed V Military Training Hospital in Rabat for bilateral knee pain, lumbosciatica, dactylitis, urethral discharge, and bloody mucus diarrhea. Radiographic and MRI examinations were atypical for RA, showing neither focal bone lesions nor intra-articular effusion. Biological tests revealed leukocytosis, an elevated sedimentation rate, and high CRP levels, while the joint fluid remained sterile. Tests detected an infection with Ureaplasma urealyticum and Chlamydia trachomatis through PCR, along with a co-infection with hepatitis C. HLA-B27 genotyping and the presence of antinuclear antibodies were also noted.
Multimorbidity representation via graph learning: A population-based study on hepatosplenic conditions in schistosomiasis-endemic areas of rural Uganda
Authors: Zhi Yin-Cong , Mpooya Simon , Kabatereine Narcis B. , Nabatte Betty , Opio Christopher K. , Chami Goylette F.
Published: October 2024

Background

The global burden of multimorbidity is increasing yet poorly understood, owing to insufficient methods available for modelling complex systems of conditions. In particular, hepatosplenic multimorbidity has been inadequately investigated.

Methods

From 17 January to 16 February 2023, we examined 3186 individuals aged 5-92 years from 52 villages across Uganda within the SchistoTrack Cohort. Point-of-care B-mode ultrasound was used to assess 45 hepatosplenic conditions. Three graph learning methods for representing hepatosplenic multimorbidity were compared including graphical lasso (GL), signed distance correlations (SDC), and co-occurrence. Graph kernels were used to identify thresholds of relevant condition inter-dependencies (edges). Graph neural networks were applied to validate the quality of the graphs by assessing their predictive performance. Clinical utility was assessed through medical expert review.

Findings

Multimorbidity was observed in 54·65% (1741/3186) of study participants, who exhibited two or more hepatosplenic conditions. Conditions of mildly fibrosed vessels were most frequently observed (>14% of individuals). Percentage thresholds were found to be 50·16% and 64·46% for GL and SDC, respectively, but could not be inferred for co-occurrence. Thresholded GL and SDC graphs had densities of 0·11 and 0·17, respectively. Both thresholded graphs were similar in predictive utility, although GL produced marginally higher AUCs under certain experiments. Both GL and SDC had significantly higher AUCs than co-occurrence. Numerous conditions were predicted with perfect sensitivity using both GL and SDC with graph convolutional network with five input conditions.

Interpretation

The most common method for multimorbidity (co-occurrence) provided an uninformative representation of hepatosplenic conditions with respect to sparsity and predictive performance. More clinically useful graphs were computed when algorithms consisted of statistical assumptions, such as graphical lasso. Future work could apply the pipeline developed here for clinically relevant multimorbidity representations.

Funding

NDPH Pump Priming Fund, John Fell Fund, Robertson Foundation, UKRI EPSRC (EP/X021793/1).
Real-Time Spatiotemporal Tracking of Infectious Outbreaks in Confined Environments with a Host-Pathogen Agent-Based System
Authors: Srinivasan Suhas , King Jeffrey , Colubri Andres , Korkin Dmitry
Published: October 2024

Deadly infection outbreaks in confined spaces, whether it is a COVID-19 outbreak on a cruise ship or at a veteran home, or measles and stomach flu outbreaks in schools, can be characterized by their rapid spread due to the abundance of common spaces, shared airways, and high population density. Preventing future infectious outbreaks and developing efficient mitigation protocols can benefit from advanced computational modeling approaches. Here, we developed an agent-based modeling approach to study the spatiotemporal dynamics of an infection outbreak in a confined environment caused by a specific pathogen and to determine effective infection containment protocols. The approach integrates the 3D geographic information system of a confined environment, the behavior of the hosts, key biological parameters about the pathogen obtained from the experimental data, and the general mechanics of host-pathogen and pathogen-fomite interactions. To assess our approach, we applied it to the historical data of infectious outbreak caused by norovirus, H1N1 influenza A, and SARS-CoV-2 viruses. As a result our model was able to accurately predict the number of infections per day, correctly identify the day when the CDC vessel sanitation protocol would be triggered, single out key biological parameters affecting the infection spread, and propose important changes to existing containment protocols, specific for different pathogens. This research not only contributes to our understanding of infection spread and containment in cruise ships but also offers insights applicable to other similar confined settings, such as nursing homes, schools, and hospitals. By providing a robust framework for real-time outbreak modeling, this study proposes new, more effective containment protocols and enhances our preparedness for managing infectious diseases and emerging pathogens in confined environments.
Neighbourhood topology unveils pathological hubs in the brain networks of epilepsy-surgery patients
Authors: Di Gaetano Leonardo , Santos Fernando A.N. , Battiston Federico , Bianconi Ginestra , Defenu Nicolò , Nissen Ida , van Straaten Elisabeth C. W. , Hillebrand Arjan , Millán Ana P.
Published: October 2024

Pathological hubs in the brain networks of epilepsy patients are hypothesized to drive seizure generation and propagation. In epilepsy-surgery patients, these hubs have traditionally been associated with the resection area: the region removed during the surgery with the goal of stopping the seizures, and which is typically used as a proxy for the epileptogenic zone. However, recent studies hypothesize that pathological hubs may extend to the vicinity of the resection area, potentially complicating post-surgical seizure control. Here we propose a neighbourhood-based analysis of brain organization to investigate this hypothesis. We exploit a large dataset of presurgical MEG (magnetoencephalography)-derived whole-brain networks from 91 epilepsy-surgery patients. Our neighbourhood-focus is two-fold. Firstly, we propose a partition of the brain regions into three sets, namely resected nodes, their neighbours, and the remaining network nodes. Secondly, we introduce generalized centrality metrics that describe the neighrbourhood of each node, providing a regional measure of hubness. Our analyses reveal that both the resection area and its neighborhood present large hub-status, but with significant variability across patients. For some, hubs appear in the resection area; for others, in its neighborhood. Moreover, this variability does not correlate with surgical outcome. These results highlight the potential of neighborhood-based analyses to uncover novel insights into brain connectivity in brain pathologies, and the need for individualized studies, with large-enough cohorts, that account for patient-specific variability.
Comparison of Cerebral ECD Perfusion in Patients with Dementia with Lewy Bodies and Parkinson’s Disease Dementia
Authors: Toyli Aili , Hung Guang-Uei , Zhao Chen , Sha Qiuying , Chiu Pai-Yi , Zhou Weihua
Published: October 2024

Dementia with Lewy bodies (DLB) and Parkinson’s Disease Dementia (PDD) are closely related neurodegenerative conditions within the Lewy body spectrum. The relationship between DLB and PDD remains debated, with ongoing discussion about whether they are distinct diseases or different manifestations of the same disorder. This study aimed to identify differences in cerebral perfusion patterns between DLB and PDD patients. Single-photon emission computed tomography (SPECT) Ethyl Cysteinate Dimer (ECD) imaging was performed on each patient, and relative tracer uptake levels across 47 regions of interest (ROIs) and 240 subregions were analyzed. A two-sided Welch’s t-test was employed to evaluate mean perfusion differences, with results further confirmed through a voxel-wise t-test mapping. After adjusting for multiple comparisons using the Benjamini-Hochberg procedure, no regions showed statistically significant differences at the 0.05 level. However, a few subregions in the visual cortices exhibited p-values just above the significance threshold, with lower mean perfusion observed in PDD patients than those with DLB. Validating these findings in larger samples could enhance scientific understanding of the differences in the pathology and progression of DLB and PDD.
Genome-wide Association Studies of Missing Metabolite Measures: Results From Two Population-based Studies
Authors: Faquih Tariq O. , Imtiaz Mohammed Aslam , Talevi Valentina , Landstra Elvire N. , van Hylckama Vlieg Astrid , Li-Gao Ruifang , Rosendaal Frits R. , Noordam Raymond , van Heemst Diana , Mook-Kanamori Dennis O. , Breteler Monique M. B. , Aziz N. Ahmad , van Dijk Ko Willems
Published: October 2024

Metabolomic studies are increasingly used for both etiological and predictive research, but frequently report missing values. We hypothesized that interindividual genetic variation may account for part of this missingness. Therefore, we performed a GWAS of missingness in measured metabolite levels using an untargeted mass spectrometry-based platform in the Netherlands Epidemiology of Obesity Study (N=594) and the Rhineland Study (N=4,165). We considered metabolites missing in 10%-90% of individuals in both cohorts (N=224). GWAS meta-analyses of these metabolites’ probability of missingness revealed 55 metabolome-wide significant associations, including 42 novel ones (p<1.58×10-10), involving 28 metabolites and 41 lead SNPs. Despite considerable pleiotropy, the majority of identified SNP-‘missing metabolite’ associations were biologically plausible, relating to beta-oxidation, bile acids, steroids, and xenobiotics metabolism. These findings suggest that missing values in metabolomics are nonrandom and partly reflect genetic variation, accounting for which is important for both clinical and epidemiological studies, especially nutritional and pharmacogenetics studies.
EEG response during sedation interruption complements behavioral assessment following severe brain injury
Authors: Maschke Charlotte , Norton Loretta , Duclos Catherine , Han Miriam , Dolhan Kira , Laforge Geoffrey , Frantz Allison , Wang Xiaoyu , Al-Hayawi Hassan , Zhang Tianyu , Lavoie Raphaël , Owen Adrian M. , Blain-Moraes Stefanie
Published: October 2024

Background and Objectives

Accurate assessment of level of consciousness and potential to recover in severe brain injury patients underpins crucial decisions in the intensive care unit but remains a major challenge for the clinical team. The neurological wake-up test (NWT) is a widely used assessment tool, but many patients’ behavioral response during a short interruption of sedation is ambiguous or absent, with little prognostic value. This study assesses the brain’s electroencephalogram response during an interruption of propofol sedation to complement behavioral assessment during the NWT to predict survival, recovery of consciousness, and long-term functional outcome in acute severe brain injury patients.

Methods

We recorded 128-channel EEG of 41 severely brain-injured patients during a clinically indicated NWT. The Glasgow Coma Scale (GCS) was used to assess behavioral responsiveness before and after interruption of sedation (GCSobserved). During the NWT, nine patients regained responsiveness, 13 patients showed ambiguous responsiveness and 19 patients were not responsive. Brain response to sedation interruption was quantified using EEG power, spatial ratios and the spectral exponent. We trained a linear regression model to identify brain patterns related to regaining behavioral responsiveness. We then applied this model to patients whose behavioral responses were ambiguous or absent, using their NWT brain responses to predict a change in behavioral response (ΔGCSpredicted). Prognostic value of the ΔGCSpredictedwas assessed using the Mann-Whitney-U test and group-separability. The patients’ survival, recovery of responsiveness, and functional outcomes were assessed up to 12 months post-recording.

Results

EEG patterns during interruption of sedation reliably predicted the GCSobservedin patients who regained responsiveness during the NWT. Electrophysiological patterns of waking-up were observed in some patients whose behavioral response was ambiguous or absent. Compared to the GCSobserved, the ΔGCSpredictedimproved separability of prognostic groups and significantly distinguished patients according to survival (U = 87, p<0.05). The EEG-trained model outperformed outcome predictions of the patients’ attending physician and predictions based on the patients’ APACHE score.

Discussion

EEG can complement behavioral assessment during the NWT to improve prognostication, inform clinicians, family members and caregivers, and to set realistic goals for treatment and therapy.
A Peer-Educator Driven Approach for Sampling Populations at Increased Mpox Risk in the Democratic Republic of the Congo: Implications for Surveillance and Response
Authors: Merritt Sydney , Halbrook Megan , Anta Yvon , Mukadi Patrick K. , Hasivirwe Vakaniaki Emmanuel , Bodisa-Matamu Tavia , Lunyanga Lygie , Kacita Cris , Kompany Jean Paul , Makangara-Cigolo Jean-Claude , Kenye Michel , Kavira Sifa , Kalonji Thierry , Linsuke Sylvie , Malembi Emile , Mukadi-Bamuleka Daniel , Sabi Liliane , Lemaille Candice , Marie Inaka , Low Nicola , Hensley Lisa E. , Hoff Nicole A. , Shongo Robert , Kindrachuk Jason , Rimoin Anne W. , Mbala-Kingebeni Placide
Published: October 2024

The epidemiological risk factors associated with mpox acquisition and severity in the Democratic Republic of the Congo (DRC) are changing. We assessed perceived mpox risk, and behavioral, clinical and sexual histories among key populations at risk of acquisition through sexual contact. Here, we describe a sampling strategy to enroll participants considered to be at increased risk for mpox infection - men who have sex with men (MSM) and sex workers (SW) - in three urban centers in the DRC. Through the combined approach of time-location sampling with peer educators and respondent-driven sampling, a mixed cohort of 2826 individuals including self-identified MSM (n = 850), SW (n = 815), both MSM and SW (n = 118) and non-MSM, non-SW individuals (n = 1043) was enrolled in Kinshasa, Kinshasa province, Kenge, Kwango province, and Goma, North Kivu province, from March-August 2024. Of these, over 90% were reached through peer educators. The odds of sampling SW individuals were higher at bars/clubs than traditional health facilities. Conversely, the odds of enrolling MSM were highest at selected health facilities. Modifications to the sampling approach were introduced in Kenge and Goma, but these did not affect the enrollment of MSM or SW participants. Ultimately, the selection of, and collaboration with, well-integrated peer educators was the most important facet of this sampling strategy. As the definitions of at-risk populations continue to change for mpox, we demonstrate a functional approach to quickly surveying otherwise hard-to-reach groups for both public health surveillance activities and response.
Genetic contributions to epigenetic-defined endotypes of allergic phenotypes in children
Authors: Thompson Emma E. , Zhong Xiaoyuan , Carbonetto Peter , Morin Andréanne , Willwerscheid Jason , Visness Cynthia M. , Bacharier Leonard B. , Kattan Meyer , O’Connor George T. , Rivera-Spoljaric Katherine , Wood Robert A. , Gold Diane R. , Khurana Hershey Gurjit K. , Johnson Christine C. , Miller Rachel L. , Seroogy Christine M. , Zoratti Edward M. , Gergen Peter J. , Levin Albert M. , Altman Matthew C. , Hartert Tina , Stephens Matthew , Jackson Daniel J. , Gern James E. , McKennan Christopher G. , Ober Carole
Published: October 2024

Background

Asthma is the most common chronic respiratory disease in children, but little is known about genetic contributions to its underlying endotypes. To address this gap, we studied the methylome, transcriptome, and genome from children with extensive phenotyping from birth.

Methods

We performed DNA methylation (DNAm) studies using the Asthma&Allergy array and RNA-sequencing in nasal mucosal cells from 284 children (age 11 years) in the Urban Environment and Childhood Asthma (URECA) birth cohort with genotypes from whole-genome sequencing. Using empirical Bayes matrix factorization on all CpGs on the array, we derived 16 DNAm signatures and tested for associations between phenotypes and gene expression. We then replicated results in two additional cohorts and estimated the heritability of phenotype-associated signatures using single-nucleotide polymorphisms (SNPs) associated with an allergic disease, and with CpGs and genes associated with the signatures.

Findings

Three DNAm signatures were associated with at least one phenotype: allergic asthma, allergic rhinitis, allergic sensitization (atopy), total IgE, exhaled nitric oxide, or blood eosinophils. The genes correlated with each of the three signatures were enriched in networks reflecting inhibited immune response to microbes, impaired epithelial barrier integrity, and activated T2 immune pathways. We replicated the signature-phenotype associations in two additional birth cohorts. The estimated joint SNP heritabilities of the signatures were 0.17 (p=0.0027), 0.30 (p=9.3x10-7), and 0.16 (p=9.0x10-7), respectively.

Interpretation

We identified three significantly heritable DNAm signatures defining asthma and allergy endotypes across diverse populations. Our study demonstrated that epigenetic patterning in airway mucosal cells reflects perturbations in underlying biological processes related to the development of asthma and allergic diseases in childhood.
Equations for Estimating Basal and Resting Metabolic Rates: A Scoping Review Protocol
Authors: Pourová Veronika , Langaufová Alena , Riad Abanoub
Published: October 2024

Objective

This scoping review aims to map the existing equations used for estimating basal and resting metabolic rates and to specify their applicability to various population groups, particularly in cases where they demonstrate higher accuracy based on age, ethnicity, and body mass index (BMI).

Methods

The proposed scoping review will be conducted in accordance with the JBI methodology for scoping reviews and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). A comprehensive search strategy has been developed to identify both published and unpublished studies. The literature search will be conducted in the following databases: MEDLINE (Ovid), EMBASE (Ovid), SportDiscus (EBSCO), and ClinicalTrials.gov. Abstracts will be screened against the inclusion criteria, and the full text of all potential studies will be reviewed by two independent researchers. Data will be extracted using a pre-designed data extraction sheet and presented in tabular form and as a narrative summary.

Results

The findings of this review will be disseminated through publication in a peer-reviewed journal and presented as an abstract at specialty conferences.

Conclusion

To the best of the authors’ knowledge, this review will be the first to comprehensively map all existing equations for both basal and resting metabolic rates. It is also a pioneering effort in synthesising evidence on the accuracy of these equations.

Open Science Framework (OSF) Registration

This project has been registered at OSF since October 3rd, 2024.https://doi.org/10.17605/OSF.IO/UD4WB
Dynamic Attentional Control Through Mixed Prefrontal Cortex Resources
Authors: Di Bello Fabio , Ceccarelli Francesco , Messinger Adam , Genovesio Aldo
Published: October 2024

Spatial attention can be either involuntarily drawn to salient, unexpected events (exogenous attention) or voluntarily directed (endogenous attention). Evidence suggests a link of both forms of attention to the (oculo)motor system. We investigated the role of the prefrontal cortex (PFC) in this relationship using a task that spatially dissociated attention from motor planning in two monkeys. PFC units flexibly encoded either the attended location or motor target, with some showing overlapping coding. Endogenous attention promotes an early engagement of these shared resources, producing two key effects: (1) it prevents interference between motor and attention systems, and (2) it regulates the extent of the exogenous shifts for attentional capture, with stronger shifts occurring when endogenous attention is weak. Overall, we show that there are separate attention and motor systems, each of which can flexibly draw on some “overlapping” resources based on environmental and internal demands.
Sex and genetic background influence intravenous oxycodone self-administration in the Hybrid Rat Diversity Panel
Authors: Duffy Eamonn P , Ward Jonathan O , Hale Luanne H , Brown Kyle T , Kwilasz Andrew J , Mehrhoff Erika A , Saba Laura M , Ehringer Marissa A , Bachtell Ryan K
Published: October 2024

Opioid Use Disorder (OUD) is an ongoing worldwide public health concern. Genetic factors contribute to multiple OUD-related phenotypes, such as opioid-induced analgesia, initiation of opioid use, and opioid dependence. Here, we present findings from a behavioral phenotyping protocol using male and female rats from 15 genetically diverse inbred strains from the Hybrid Rat Diversity Panel (HRDP). We used a self-administration paradigm to measure the acquisition of oxycodone intake during ten 2-hour sessions and escalation of oxycodone use during ten 12-hour sessions. During both the acquisition and escalation phases of self-administration, we observed that genetic background and sex influence oxycodone intake. The heritability of oxycodone intake phenotypes ranged between 0.26 to 0.54, indicating that genetic background plays a major role in the variability of oxycodone consumption. Genetic background and sex also influenced additional phenotypes recorded during oxycodone self-administration including lever discrimination and timeout responding. The genetic contribution to these traits was slightly more moderate, with heritability estimates ranging between 0.25 to 0.42. Measures of oxycodone intake were highly positively correlated between acquisition and escalation phases. Interestingly, the efficacy of oxycodone analgesia was positively correlated with oxycodone intake during the escalation phase, indicating that the initial behavioral responses to oxycodone may predict self-administration phenotypes. Together, these data demonstrate that sex and genetic background are major contributors to oxycodone self-administration phenotypes.
Haematobiochemical Alterations and Lesion Characterization Induced by Haemonchosis in Sheep Slaughtered at Gondar ELFORA Abattoir, North West Ethiopia
Authors: Malede Birhan Anagaw , Kebede Mersha Chanie , Berihun Asnakew Mulaw , Mekonnen Muluken Yayeh , Yesuf Mohammed , Mitiku Tadegegn , Birhan Mastewal , Kenubih Ambaye , Temesgen Abraham Belete
Published: October 2024

Haemonchosis is a major gastrointestinal parasitic infection in sheep caused byHaemonchus contortus. An abattoir-based cross-sectional study was conducted from January to September 2024 to assess the Haematobiochemical alterations and lesion characterization induced by Haemonchosis in sheep slaughtered at the Gondar ELFORA abattoir. The study involved 60 male local breed sheep, divided into 30 infected and 30 non-infected controls. The selection process involved postmortem examination of the abomasum tissues, incision, palpation, and visual inspection. Blood samples were taken for hematology and serum biochemical profiles, and a three cm tissue sample with typicalHaemonchus contortuslesions was also taken. The study found significant reductions in hemoglobin, hematocrit, corpuscular volume, hemoglobin, and red blood cell counts in the infected group compared to the non-infected group. However, white blood cells, monocytes, neutrophils, and eosinophils were significantly higher in the infected group. Biochemical parameters showed significant reductions in total protein, albumin, globulin, and albumin to globulin ratio in the infected group. Erythrocyte indices indicated microcytic normochromic anemia. Gross examination revealed hemorrhages, dark brown abomasal contents, blood streaks, and a nodular lesion. Microscopic analysis revealed tissue-dwelling worms, submucosal hemorrhage, mucosal gland hyperplasia, thickened muscularis, and hyperplastic abomasal glands. The alterations in haematobiochemical parameters support the findings from gross and microscopic lesions. Thus, integrating haematobiochemical analysis with gross and microscopic lesion characterization improves the diagnosis of haemonchosis. Due to hypoproteinemia observed, it is advisable to supplement helminth-infected animals with protein-rich feeds, such as legumes.
Genomic Analysis ofSalmonella entericafrom cattle, beef and humans in the Greater Tamale Metropolis of Ghana
Authors: Sunmonu Gabriel Temitope , Saba Courage Kosi Setsoafia , Odih Erkison Ewomazino , Bright Opoku , Osei Eric Edem Yao , Mensah Alfred , Abdallah Saeed , Alhassan Abdul-Razak , Kpordze Stephen Wilson , Akinlabi Olabisi C , Oaikhena Anderson O , Egyir Beverly , Okeke Iruka N
Published: October 2024

Salmonella entericais a bacterial foodborne pathogen notorious for infecting humans and animals. Proper control ofSalmonellarequires routine surveillance and interventions across the food-production chain. However, due to limited resources the dynamics and transmission of non-typhoidalSalmonellaserotypes remain poorly understood in several African settings, including within Ghana. Here, we employed bacterial culture and whole genome sequencing (WGS) to investigate the prevalence, virulence and antimicrobial resistance determinants ofSalmonella entericaisolates from beef, cattle blood and human patient stool in Greater Tamale Metropolis, Ghana. Enrichment and culture of the specimens yielded 62 isolates in total from beef (31), bovine blood (28) and human diarrhoeal specimens (3). We identified at least 15 STs and 18 differentSalmonellaserovars. The most common serovars detected were Poona (n=13), Montevideo (n=10) and Poano (n=7) with S. Montevideo being the most common from cattle blood. Thirty-two isolates belonged to novel sequence types (STs), with ST2609 (n=9) being most common. Four raw beef isolates harboured at least one gene conferring resistance to beta-lactam (blaTEM-1), chloramphenicol (catA), fosfomycin (fosA7), quinolone (qnrD1) or tetracycline (tet(A)). Eight isolates carried at an IncF, IncI and/orCol3M plasmid replicon. This study recoveredSalmonella, often belonging to previously undocumented STs, at high frequencies from cattle and beef and demonstrated that isolates from human diarrhoeal patients are closely related to bovine isolates. The data highlight the need for broader and sustained surveillance and the urgent need for food safety interventions in Ghana.
Sexual selection matters in genetic rescue, but productivity benefits fade over time; a multi-generation experiment to inform conservation
Authors: West George , Pointer Michael , Nash Will , Lewis Rebecca , Gage Matt J.G. , Richardson David S.
Published: October 2024

Globally, many species are threatened by population decline because of anthropogenic changes which leads to population fragmentation, genetic isolation, and inbreeding depression. Genetic rescue, the controlled introduction of genetic variation, is a method used to potentially relieve such effects in small populations. However, without understanding how the characteristics of rescuers impact rescue attempts interventions run the risk of being sub-optimal, or even counterproductive. We use the Red Flour Beetle (Tribolium castaneum) to test the impact of rescuer sex, and sexual selection background, on population productivity. We record the impact of genetic rescue on population productivity in 24/36 replicated populations for ten generations following intervention. We find little or no impact of rescuer sex on the efficacy of rescue but show that a background of elevated sexual selection makes individuals more effective rescuers. In both experiments, rescue effects diminish 6-10 generations after the rescue. Our results confirm that the efficacy of genetic rescue can be influenced by characteristics of the rescuers and that the level of sexual selection in the rescuing population is an important factor. We show that any increase in fitness associated with rescue may last for a limited number of generations, suggesting implications for conservation policy and practice.
Unveiling the role of miRNAs from MSC-EVs in neuroinflammation and behavioral impairments induced by chronic alcohol consumption
Authors: Mellado Susana , Touahri Najoua , Montagud-Romero Sandra , Perpiñá-Clérigues Carla , García-García Francisco , Moreno-Manzano Victoria , Guerri Consuelo , Arias Marta Rodríguez- , Pascual María
Published: October 2024

Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) have emerged as a promising form of regenerative and immunomodulatory therapy; indeed, micro (mi)RNAs contained within MSC-EVs modulate target gene expression and impact disease-associated pathways. Chronic alcohol consumption results in neuroinflammation, brain damage, and impaired cognition; in this study, we asked whether the repeated intravenous administration of MSC-EVs could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in mice. MSC-EVs diminished the increased binding of a micro-positron emission tomography tracer (18F-FDG) when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice. MSC-EV administration protected against ethanol-induced proinflammatory gene upregulation, cognitive dysfunction, and addictive-like behavior. miRNA sequencing data from MSC-EVs helped to reveal the elevated expression of EV-derived miR-483-5p and miR-140-3p in the brains of ethanol-treated mice following MSC-EV administration. In addition, MSC-EVs modulated the expression of pro-inflammatory-related miRNA target genes (e.g., Socs3, Tnf, Mtor, Atf6) in the brains of ethanol-treated mice. These results suggest that MSC-EVs could function as a neuroprotective therapy to ameliorate the neuroinflammation, cognitive dysfunction, and addictive-like behavior associated with chronic alcohol consumption.
Fatty acid desaturation guides cellular decisions between ferroptosis and cellular senescence
Authors: Kuehnemann Chisaka , Jezak Samantha , Mogck Bronwyn , Kura Niharika , Che Yuheng , Vaittinen Maija , Siokas Ioannis , Tariq Rushmeen , Deshpande Sharvari , Guthrie Carlyn , Tan Xuejuan , Aimontche Eliezer , Zheng Tong , Greenberg Andrew S. , Wang Xiang-Dong , Kitazawa Koji , Dolnikowsi Gregory , Cheng Yong , Matthan Nirupa R. , Ramanthan Arvind , Pihlajamaki Jussi , Korstanje Ron , Wiley Christopher D.
Published: October 2024

When subject to damage or stress, cells develop responses in order to maintain tissue homeostasis. Two such decisions are ferroptosis and cellular senescence, but how cells decide between these outcomes remains unclear. Here we show that senescent cells increase levels of multiple membrane-bound polyunsaturated fatty acids (PUFAs), but a specific PUFA, dihomo-gamma-linolenic acid (DGLA, 20:3ω-3) is reduced. Exogenous repletion of DGLA or inhibition of delta-5-desaturase, the enzyme that metabolizes DGLA, instead results in cell death by ferroptosis. Senescent cells had elevated levels of other fezzroptosis sensitizers, including labile iron and expression of lipoxygenases – but also increased Gpx4 levels to prevent ferroptosis. Oral DGLA lowered senescent cell burden in aged mice and improved age-related functional outcomes. Finally, obese humans with lowered DGLA desaturation rates showed lower markers of adipose tissue senescence. Together, our data implicate DGLA and its desaturation as a major driver of decisions between senescence and ferroptosis.
Bottlebrush polymers with sequence-controlled backbones for enhanced oligonucleotide delivery
Authors: Wei Yun , Chen Peiru , Ren Mengqi , Li Deng , Lin Jiachen , Sun Tingyu , Wang Yuyan , Yang Shaobo , Nenopoulos Christopher , Oetheimer Christopher , Li Yao , Xue Chenyang , Minkara Mona , Zhang Ke
Published: October 2024

The clinical translation of oligonucleotide-based thera-peutics continues to encounter challenges in delivery. In this study, we introduce a novel class of delivery vehicles for oligonucleotides, which are based on polyethylene glycol (PEG) bottlebrush polymers with sequence-defined backbones. Using solid-phase synthesis and bespoke phosphoramidites, the oligonucleotide and the polymer backbone can both be assembled on the solid support. The synthesis allows chemical modifiers such as carbon 18 (C18) units to be incorporated into the backbone in specific patterns to modulate the cell-materials interactions. Subsequently, PEG side chains were grafted onto the polymer segment of the resulting polymer-oligonucleotide conjugate, yielding bottlebrush polymers. We report an optimal pattern of the C18modifier that leads to improved cellular uptake, plasma phar-macokinetics, biodistribution, and antisense activity in vivo. Our results provide valuable insights into the pacDNA structure-property relationship and suggest a possibility of tuning the polymer backbone to meet the specific delivery requirements of various diseases.

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Out of the single-neuron straitjacket: neurons within assemblies change selectivity and their reconfiguration underlies dynamic coding
Authors: Londei Fabrizio , Ceccarelli Francesco , Arena Giulia , Ferrucci Lorenzo , Russo Eleonora , Brunamonti Emiliano , Genovesio Aldo
Published: October 2024

We investigated cell assemblies in the frontal cortex of macaques during two discrimination tasks. Focusing on the period of goal-action transformation, we extracted spikes fired during assembly activation from the full neural activity and showed that the contribution of a neuron to assembly coding, when it coordinates with other assembly neurons, differs from its coding in isolation. Neurons with their flexible participation to multiple assemblies contributed to the encoding of new information not encoded by the neurons alone. Even non-discriminative neurons acquired selectivity as part of the collective activity of the assemblies. Thus, neurons in their assemblies process distinct information for various purposes as a chess simul master, playing on multiple chessboards. The reconfiguration of the participation of the neurons into different assemblies in the goal-action transformation process translated into a dynamic form of coding, whereas minimal reconfiguration was associated with the static goal coding of the memory period.
LIET Model: Capturing the kinetics of RNA polymerase from loading to termination
Authors: Stanley Jacob T. , Barone Georgia E.F. , Townsend Hope A. , Sigauke Rutendo F. , Allen Mary A. , Dowell Robin D.
Published: October 2024

Transcription by RNA polymerases is an exquisitely regulated step of the central dogma. Transcription is the primary determinant of cell-state, and most cellular perturbations impact transcription by altering polymerase activity. Thus, detecting changes in polymerase activity yields insight into most cellular processes. Nascent run-on sequencing provides a direct readout of polymerase activity, but no tools exist to model this activity at genes. We focus on RNA polymerase II—responsible for transcribing protein-coding genes. We present the first model to capture the complete process of gene transcription. For individual genes, this model parameterizes each distinct stage of transcription—Loading, Initiation, Elongation, andTermination, hence LIET—in a biologically interpretable Bayesian mixture, which is applied to nascent run-on data. Our improved modeling ofLoading/Initiationdemonstrates these are characteristically different between sense and antisense strands. Applying LIET to 24 human cell-types, our analysis indicates the position of dissociation (the last step ofTermination) appears to be highly consistent, indicative of a highly regulated process. Furthermore, applying LIET to perturbation experiments, we demonstrate its ability to detect specific changes in pausing (5′end), strand-bias, and dissociation location (3′end)—opening the door to differential assessment of transcription at individual stages of individual genes.