bluuebunny/crossref_metadata_2025_split huggingface dataset:
4′-Fluorouridine inhibits alphavirus replication and infection
in vitro
and
in vivo
Authors: Yin Peiqi , May Nicholas A. , Lello Laura Sandra , Fayed Atef , Parks M. Guston , Drobish Adam M. , Wang Sainan , Andrews Meghan , Sticher Zachary , Kolykhalov Alexander A. , Natchus Michael G. , Painter George R. , Merits Andres , Kielian Margaret , Morrison Thomas E. 
Published: May 2024

ABSTRACT

Chikungunya virus (CHIKV) is an enveloped, positive-sense RNA virus that has re-emerged to cause millions of human infections worldwide. In humans, acute CHIKV infection causes fever and severe muscle and joint pain. Chronic and debilitating arthritis and joint pain can persist for months to years. To date, there are no approved antivirals against CHIKV. Recently, the ribonucleoside analog 4′-fluorouridine (4′-FlU) was reported as a highly potent orally available inhibitor of SARS-CoV-2, respiratory syncytial virus, and influenza virus replication. In this study, we assessed 4′-FlU’s potency and breadth of inhibition against a panel of alphaviruses including CHIKV, and found that it broadly suppressed alphavirus production in cell culture. 4′-FlU acted on the viral RNA replication step, and the first 4 hours post-infection were the critical time for its antiviral effect.
In vitro
replication assays identified nsP4 as the target of inhibition.
In vivo
, treatment with 4′-FlU reduced disease signs, inflammatory responses, and viral tissue burden in mouse models of CHIKV and Mayaro virus infection. Treatment initiated at 2 hours post-infection was most effective; however, treatment initiated as late as 24–48 hours post-infection produced measurable antiviral effects in the CHIKV mouse model. 4′-FlU showed effective oral delivery in our mouse model and resulted in the accumulation of both 4′-FlU and its bioactive triphosphate form in tissues relevant to arthritogenic alphavirus pathogenesis. Together, our data indicate that 4′-FlU inhibits CHIKV infection
in vitro
and
in vivo
and is a promising oral therapeutic candidate against CHIKV infection.

IMPORTANCE

Alphaviruses including chikungunya virus (CHIKV) are mosquito-borne positive-strand RNA viruses that can cause various diseases in humans. Although compounds that inhibit CHIKV and other alphaviruses have been identified
in vitro
, there are no licensed antivirals against CHIKV. Here, we investigated a ribonucleoside analog, 4′-fluorouridine (4′-FlU), and demonstrated that it inhibited infectious virus production by several alphaviruses
in vitro
and reduced virus burden in mouse models of CHIKV and Mayaro virus infection. Our studies also indicated that 4′-FlU treatment reduced CHIKV-induced footpad swelling and reduced the production of pro-inflammatory cytokines. Inhibition in the mouse model correlated with effective oral delivery of 4′-FlU and accumulation of both 4′-FlU and its bioactive form in relevant tissues. In summary, 4′-FlU exhibits potential as a novel anti-alphavirus agent targeting the replication of viral RNA.
Genomic profiling and characterization of ocular
Chlamydia trachomatis
reference strain B/HAR36
Authors: Ghasemian Ehsan , Holland Martin J. 
Published: May 2024

ABSTRACT

The human pathogen
Chlamydia trachomatis
has multiple serovariants that have distinct organotropisms. We recently revised genomic sequence data linked to ocular reference strain, B/HAR36. Now linked to its correct genomic data in the European Nucleotide Archive, we describe its genomic features.
A survey of multiple candidate probiotic bacteria reveals specificity in the ability to modify the effects of key wound pathogens
Authors: Alhubail Muna , McBain Andrew J. , O'Neill Catherine A. 
Published: May 2024

ABSTRACT

We have evaluated the inhibitory effects of supernatants and lysates derived from several candidate probiotics, on the growth and biofilm formation of wound pathogens, and their ability to protect human primary epidermal keratinocytes from the toxic effects of pathogens. Supernatants (neutralized and non-neutralized) and lysates (
via
sonication) from
Lactiplantibacillus plantarum, Limosilactobacillus reuteri, Bifidobacterium longum, Lacticaseibacillus rhamnosus
GG, and
Escherichia coli
Nissle 1917 were tested for their inhibitory effects against
Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa,
and
Acinetobacter baumanni
. The supernatants of
L. plantarum, L. rhamnosus, B. longum,
and
L. rhamnosus
GG reduced the growth of
S. aureus, E. coli,
and
A. baumanni. B. longum
additionally inhibited
P. aeruginosa
growth. However, neutralized
Lactobacillus
supernatants did not inhibit growth and in some cases were stimulatory. Lysates of
L. plantarum
and
L. reuteri
inhibited
S. pyogenes
while
B. longum
lysates inhibited
E. coli
and
S. aureus
growth.
E. coli
Nissle 1917 lysates enhanced the growth of
S. pyogenes
and
P. aeruginosa
. Biofilm formation by
E. coli
was reduced by lysates of
L. reuteri
and neutralized supernatants of all candidate probiotics.
P. aeruginosa
biofilm formation was reduced by
E. coli
Nissle supernatant but increased by
L. plantarum, L. reuteri,
and
Bifidobacterium longum
lysates.
L. reuteri
decreased the toxic effects of
S. aureus
on keratinocytes while
E. coli
Nissle 1917 lysates protected keratinocytes from
S. pyogenes
toxicity. In conclusion, lactobacilli and
E. coli
Nissle lysates confer inhibitory effects on pathogenic growth independently of acidification and may beneficially alter the outcome of interactions between host cell-pathogen in a species-specific manner.

IMPORTANCE
One of the attributes of probiotics is their ability to inhibit pathogens. For this reason, many lactobacilli have been investigated for their effects as potential topical therapeutics against skin pathogens. However, this field is in its infancy. Even though probiotics are known to be safe when taken orally, the potential safety concerns when applied to potentially compromised skin are unknown. For this reason, we believe that extracts of probiotics will offer advantages over the use of live bacteria. In this study, we have surveyed five candidate probiotics, when used as extracts, in terms of their effects against common wound pathogens. Our data demonstrate that some probiotic extracts promote the growth of pathogens and highlight the need for careful selection of species and strains when probiotics are to be used topically.
Designing a smallpox B-cell and T-cell multi-epitope subunit vaccine using a comprehensive immunoinformatics approach
Authors: Yu Changqing , Wu Qi , Xin Jiuqing , Yu Qiujuan , Ma Zhixin , Xue Mengzhou , Xu Qingyuan , Zheng Chunfu 
Published: May 2024

ABSTRACT

Smallpox is a highly contagious human disease caused by the variola virus. Although the disease was eliminated in 1979 due to its highly contagious nature and historical pathogenicity, with a mortality rate of up to 30%, this virus is an important candidate for biological weapons. Currently, vaccines are the critical measures to prevent this virus infection and spread. In this study, we designed a peptide vaccine using immunoinformatics tools, which have the potential to activate human immunity against variola virus infection efficiently. The design of peptides derives from vaccine-candidate proteins showing protective potential in vaccinia WR strains. Potential non-toxic and nonallergenic T-cell and B-cell binding and cytokine-inducing epitopes were then screened through a priority prediction using special linkers to connect B-cell epitopes and T-cell epitopes, and an appropriate adjuvant was added to the vaccine construction to enhance the immunogenicity of the peptide vaccine. The 3D structure display, docking, and free energy calculation analysis indicate that the binding affinity between the vaccine peptide and Toll-like receptor 3 is high, and the vaccine receptor complex is highly stable. Notably, the vaccine we designed is obtained from the protective protein of the vaccinia and combined with preventive measures to avoid side effects. This vaccine is highly likely to produce an effective and safe immune response against the variola virus infection in the body.

IMPORTANCE
In this work, we designed a vaccine with a cluster of multiple T-cell/B-cell epitopes, which should be effective in inducing systematic immune responses against variola virus infection. Besides, this work also provides a reference in vaccine design for preventing monkeypox virus infection, which is currently prevalent.
Deep learning-based model for difficult transfemoral access prediction compared with human assessment in stroke thrombectomy
Authors: Canals Pere , Garcia-Tornel Alvaro , Requena Manuel , Jabłońska Magda , Li Jiahui , Balocco Simone , Díaz Oliver , Tomasello Alejandro , Ribo Marc 
Published: May 2024

BackgroundIn mechanical thrombectomy (MT), extracranial vascular tortuosity is among the main determinants of procedure duration and success. Currently, no rapid and reliable method exists to identify the anatomical features precluding fast and stable access to the cervical vessels.MethodsA retrospective sample of 513 patients were included in this study. Patients underwent first-line transfemoral MT following anterior circulation large vessel occlusion stroke. Difficult transfemoral access (DTFA) was defined as impossible common carotid catheterization or time from groin puncture to first carotid angiogram >30 min. A machine learning model based on 29 anatomical features automatically extracted from head-and-neck computed tomography angiography (CTA) was developed to predict DTFA. Three experienced raters independently assessed the likelihood of DTFA on a reduced cohort of 116 cases using a Likert scale as benchmark for the model, using preprocedural CTA as well as automatic 3D vascular segmentation separately.ResultsAmong the study population, 11.5% of procedures (59/513) presented DTFA. Six different features from the aortic, supra-aortic, and cervical regions were included in the model. Cross-validation resulted in an area under the receiver operating characteristic (AUROC) curve of 0.76 (95% CI 0.75 to 0.76) for DTFA prediction, with high sensitivity for impossible access identification (0.90, 95% CI 0.81 to 0.94). The model outperformed human assessment in the reduced cohort [F1-score (95% CI) by experts with CTA: 0.43 (0.37 to 0.50); experts with 3D segmentation: 0.50 (0.46 to 0.54); and model: 0.70 (0.65 to 0.75)].ConclusionsA fully automatic model for DTFA prediction was developed and validated. The presented method improved expert assessment of difficult access prediction in stroke MT. Derived information could be used to guide decisions regarding arterial access for MT.
Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China
Authors: Rahman Mohammad L , Breeze Charles E , Shu Xiao-Ou , Wong Jason Y Y , Blechter Batel , Cardenas Andres , Wang Xuting , Ji Bu-Tian , Hu Wei , Cai Qiuyin , Hosgood H Dean , Yang Gong , Shi Jianxin , Long Jirong , Gao Yu-Tang , Bell Douglas A , Zheng Wei , Rothman Nathaniel , Lan Qing 
Published: May 2024

BackgroundThe aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted.MethodsWe conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women’s Health Study and Shanghai Men’s Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis.ResultsOur study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10−8. These DMPs were identified as cg09198866 (MYH9;TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34).ConclusionsWhile replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.
Prevalence of nutritional risk and malnutrition in hospitalized patients: a retrospective, cross-sectional study of single-day screening
Authors: Alvarez-Altamirano Karolina , Bejarano-Rosales Mónica P. , González-Rodríguez Bárbara Kassandra , Mondragón-Nieto Grissel , Alatriste-Ortiz Gabriela , Noguez Liz J. Jiménez , Gutiérrez-Salmeán Gabriela , Fuchs-Tarlovsky Vanessa 
Published: May 2024

Hospital malnutrition remains a significant public health issue, particularly in developing countries. The Global Leadership Initiative on Malnutrition (GLIM) proposed homogenizing criteria to standardize malnutrition diagnosis. This study aimed to retrospectively determine the prevalence of nutritional risk and malnutrition diagnoses among hospitalized patients using the Nutritional Risk Screening (NRS)-2002 screening instrument and the GLIM criteria, respectively. We conducted a retrospective, cross-sectional study from nutritional records of patients hospitalized in a single centre 2021. Nutrition data from records included medical diagnosis, gender, length of stay, age, weight, height, body mass index, weight loss, calf circumference, and middle upper arm circumference. Nutritional risk and malnutrition were evaluated using NRS-2002 and GLIM criteria. Its concordance was further evaluated by using a Kappa test. The study included 616 records of patients; 52.3% ( n = 322) of the population were male. The prevalence of nutritional risk, according to NRS-2002, was 69.5% ( n = 428). Nutritional risk as well as malnutrition diagnosis according to GLIM criteria was observed in 87.8% ( n = 374) of patienttritional risk and malnutrition were evaluated using NRS-2002 and GLIM criteria. Its concordance was further evaluated by using a Kappa test. Ws. Tools showed a strong concordance (κ= 0.732). All anthropometric data, except for height, were found to be significantly different between patients with moderate and severe malnutrition ( p < 0.05). Our findings highlight a high prevalence of malnutrition in this group of hospitalized patients in Mexico. NRS-2002 demonstrated good agreement with the diagnosis of malnutrition according to GLIM criteria and could be considered part of the straightforward two-step approach for malnutrition; however, further studies are needed.
Efficient Decoding of Affective States from Video-elicited EEG Signals: An Empirical Investigation
Authors: Latifzadeh Kayhan , Gozalpour Nima , Traver V. Javier , Ruotsalo Tuukka , Kawala-Sterniuk Aleksandra , Leiva Luis A 
Published: May 2024

Affect decoding through brain-computer interfacing (BCI) holds great potential to capture users’ feelings and emotional responses via non-invasive electroencephalogram (EEG) sensing. Yet, little research has been conducted to understand
efficient
decoding when users are exposed to
dynamic
audiovisual contents. In this regard, we study EEG-based affect decoding from videos in arousal and valence classification tasks, considering the impact of signal length, window size for feature extraction, and frequency bands. We train both classic Machine Learning models (SVMs and
k
-NNs) and modern Deep Learning models (FCNNs and GTNs). Our results show that: (1) affect can be effectively decoded using less than 1 minute of EEG signal; (2) temporal windows of 6 and 10 seconds provide the best classification performance for classic Machine Learning models but Deep Learning models benefit from much shorter windows of 2 seconds; and (3) any model trained on the Beta band alone achieves similar (sometimes better) performance than when trained on all frequency bands. Taken together, our results indicate that affect decoding can work in more realistic conditions than currently assumed, thus becoming a viable technology for creating better interfaces and user models.
Diet Modulates the Gut Microbiome, Metabolism, and Mammary Gland Inflammation to Influence Breast Cancer Risk
Authors: Arnone Alana A. , Wilson Adam S. , Soto-Pantoja David R. , Cook Katherine L. 
Published: May 2024

Abstract
Several studies indicate a strong link between obesity and the risk of breast cancer. Obesity decreases gut microbial biodiversity and modulates Bacteroidetes-to-Firmicutes phyla proportional abundance, suggesting that increased energy-harvesting capacity from indigestible dietary fibers and elevated lipopolysaccharide bioavailability may promote inflammation. To address the limited evidence linking diet-mediated changes in gut microbiota to breast cancer risk, we aimed to determine how diet affects the microbiome and breast cancer risk. For ten weeks, female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut oil, lard + flaxseed oil, and lard + safflower oil). Fecal 16S sequencing was performed for each group. Diet shifted fecal microbiome populations and modulated mammary gland macrophage infiltration. Fecal-conditioned media shifted macrophage polarity and inflammation. In our DMBA-induced breast cancer model, diet differentially modulated tumor and mammary gland metabolism. We demonstrated how dietary patterns change metabolic outcomes and the gut microbiota, possibly contributing to breast tumor risk. Furthermore, we showed the influence of diet on metabolism, inflammation, and macrophage polarity. This study suggests that dietary–microbiome interactions are key mediators of breast cancer risk.
Prevention Relevance: Our study demonstrates the impact of diet on breast cancer risk, focusing on the interplay between diet, the gut microbiome, and mammary gland inflammation.
Metapicture: pintura de história em quadrinhos
Authors: Paula Marcus Vinicius de , Lima Alberto K. 
Published: May 2024

It uses the metalinguistic strategy to reflect on the relationship between narrative in figurative painting and comics. Therefore, it treats the potential of self-reflexive images and their theoretical-critical abilities using the concept of metapicture, coined by W. J. T. Mitchell. The second step looks for examples in art history that prove the importance of self-reflective experiences for the theory of painting. Then, it shows how comics expanded the investigative possibilities of metapicture through humor. Afterwards, some examples from MAD magazine are used to argue that, beyond the self-reflection of a visual language, there is a great critical potential in the projection of one visual language over the other. Finally, the rich experiences in comics that have called academic pictorial language into question are presented.
Beneficial Effects of Oral Carbon Monoxide on Doxorubicin‐Induced Cardiotoxicity
Authors: Alves de Souza Rodrigo W. , Voltarelli Vanessa , Gallo David , Shankar Sidharth , Tift Michael S. , Young Mark , Gomperts Edward , Gomperts Andrew , Otterbein Leo E. 
Published: May 2024

Background
Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI‐002) that can be easily self‐administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract.

Methods and Results
HBI‐002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI‐002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI‐002 had a 6.3‐fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase‐1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI‐002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI‐002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function.

Conclusions
These findings strongly support using HBI‐002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.
Association of Blood Copper With the Subclinical Carotid Atherosclerosis: An Observational Study
Authors: Zhou Denglu , Mao Qi , Sun Yapei , Cheng Hao , Zhao Jianhua , Liu Qingsong , Deng Mengyang , Xu Shangcheng , Zhao Xiaohui 
Published: May 2024

Background
Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear.

Methods and Results
This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty‐five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal‐progressively‐adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021–1.238], relative risk according to per interquartile increment was 1.039 [1.008–1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper–cadmium–lead mixture on subclinical carotid plaque presence.

Conclusions
Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.