bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory effects of yeast-derived vacuoles on LPS-induced murine macrophage activation
Authors: Lee Su-Min , Kim Yang-Hoon , Min Jiho 
Published: September 2023

ABSTRACT

Saccharomyces cerevisiae
is a single-celled fungal microorganism.
S. cerevisiae
-derived vacuoles are closely related to mammalian lysosomes, which play a role in the degradation of macromolecules by various hydrolytic enzymes. This study evaluated the anti-inflammatory efficacy of
S. cerevisiae
-vacuoles by inhibiting inflammatory mediators induced by lipopolysaccharide (LPS). The results showed that treatment with 5, 10, and 20 µg/mL of
S. cerevisiae
-derived vacuoles almost completely inhibited the LPS-induced expression of iNOS protein and mRNA. Moreover, vacuoles significantly reduced the mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in LPS-stimulated macrophages compared to the control cells. The immunofluorescence analysis confirmed that
S. cerevisiae
-derived vacuoles inhibited the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated cells. Taken together, the treatment with
S. cerevisiae
-derived vacuoles alone activated macrophages, but LPS-activated macrophages modulated pro-inflammatory mediators by downregulating the NF-κB pathway. These results suggest that
S. cerevisiae
-derived vacuoles may have therapeutic potential in the treatment of inflammatory diseases. In conclusion, our study provides new insights into the immunomodulatory effects of
S. cerevisiae
-derived vacuoles and their potential as a novel anti-inflammatory agent.

IMPORTANCE

This study investigates the potential of using vacuoles derived from the yeast
Saccharomyces cerevisiae
as a new anti-inflammatory therapy. Inflammation is a natural response of the immune system to invading pathogens, but when it is dysregulated, it can lead to chronic diseases. The researchers found that treating macrophages with vacuoles significantly reduced the production of pro-inflammatory cytokines and iNOS, markers of inflammation when they were stimulated with lipopolysaccharide. The study also showed that vacuoles inhibited the NF-κB signaling pathway, which is involved in the induction of pro-inflammatory cytokines in macrophages. These findings suggest that
S. cerevisiae
-derived vacuoles may have potential as a new therapeutic agent for regulating the inflammatory response in various diseases. Further studies are needed to evaluate the efficacy and safety of vacuoles
in vivo
and to elucidate the underlying mechanisms of their anti-inflammatory effects.
The inhibitory effect of berberine chloride hydrate on
Streptococcus mutans
biofilm formation at different pH values
Authors: Zhou Yang , Liu Zhuoying , Wen Jie , Zhou Yan , Lin Huancai 
Published: September 2023

ABSTRACT

Streptococcus mutans
(
S. mutans
) is one of the major cariogenic bacteria of dental caries owing to its ability to adhere to tooth surfaces and biofilm formation. Berberine chloride hydrate (BH), a quaternary ammonium salt alkaloid, has diverse pharmacological efforts against microorganisms. However, the effect of BH on
S. mutans
biofilm has not been reported. Considering that berberine is a quaternary ammonium salt alkaloid, which needs to adapt to a large variation in pH values and the acid resistance of
S. mutans
, we employed three groups including pH 5 (acidic), pH 8 (alkaline), and unprocessed group (neutral) to examine the antibiofilm activities of BH against
S. mutans
during different pH values. In this study, we found BH effectively suppresses
S. mutans
biofilm formation as well as its cariogenic virulence including acid production and EPS synthesis significantly, and the inhibitory effort was reduced under acidic condition whereas elevated under alkaline condition. In addition, we preliminarily explored the influence of pH values on the structural stability and biosafety of BHas well as the underlying mechanism of inhibition of
S. mutans
biofilm formation with BH. Our study showed BH could maintain a good structural stability and low toxicity to erythrocytes at different pH values. And BH could downregulate the expression of
srtA, spaP,
and
gbpC,
which play critical roles in the adhesion process, promoting bacterial colonization and biofilm formation. Furthermore,
comX
and
ldh
expression levels were downregulated in BH-treated group, which might explain its inhibitory effect on acid production.

IMPORTANCE

Dental caries is a common chronic detrimental disease, which could cause a series of oral problem including oral pain, difficulties in eating, and so on. Recently, many natural products have been considered as fundamental sources of therapeutic drugs to prevent caries. Berberine as a plant extract showed good antibiofilm abilities against microorganism. Our study focuses on its antibiofilm abilities against
S. mutans,
which was defined as major cariogenic bacterium and explored the role of pH values and possible underlying mechanisms in the inhibitory effect of BH on
S. mutans
biofilm formation. This study demonstrated a promising prospect for BH as an adjuvant drug in the prevention and management of dental caries.
Middle Ura Association of Organic-Walled Microfossils: the Lower Vendian of the Patom Basin, Siberia
Authors: Vorob’eva N. G. , Petrov P. Yu. 
Published: September 2023

Abstract
A new assemblage of Early Vendian (Middle Ediacaran) microfossils, including acanthomorphic acritarchs and various filamentous remains, as well as sphaeromorphic striated vesicles of Valeria, which are not characteristic of deposits of this age, is described from the Ura Formation of the Dal’nyaya Taiga Group of the Patom Basin. A new species of acanthomorphs Hocosphaeridium crispum sp. nov. is recognised. The Ediacaran eukaryotic phytoplankton taphocoenoses are shown to be selectively restricted to the open-sea proximal facies of the inner ramp.
Understanding why and how youth-friendly health services improve viral load suppression among adolescents and young people living with HIV in Nigeria: realist evaluation with qualitative comparative analysis
Authors: Badejo Okikiolu , Nöstlinger Christiana , Wouters Edwin , Laga Marie , Okonkwo Prosper , Jwanle Plang , Van Belle Sara 
Published: September 2023

IntroductionYouth-friendly health service (YFHS) approaches are essential to better outcomes for young people. We evaluated attainment of viral load suppression among young people living with HIV (YPLHIV) enrolled in an HIV treatment programme implementing YFHS models in Nigeria.MethodsA realist evaluation using qualitative and quantitative programme data from 10 implementing health facilities. We used qualitative information to explore how and why viral load suppression was attained across different settings and quantitative data to describe patterns and associations between youth-friendly structures and processes of care, care retention and viral load suppression. To consolidate the theories, we used qualitative comparative analysis to identify the necessary and sufficient conditions for attaining viral load suppression, using 30 YPLHIV as cases.ResultsBetween baseline (2018) and study-end (May 2022), viral load suppression coverage increased in 8 of the 10 study facilities. The number of facilities with viral load suppression coverage ≥90% rose from two to seven, while one facility remained unchanged, and another had a decline in coverage. Among the 30 selected YPLHIV cases, 18 had viral load suppression during the first test and 24 at the second test. However, viral load suppression attainment varied in different contexts. We identified the different YFHS interventions and key mechanisms that influenced viral load suppression in different contexts.ConclusionYFHS interventions can improve young people’s engagement with HIV services, but their effectiveness depends on specific mechanisms and contextual factors influencing their response to interventions. By exploring how and why viral load suppression was attained in different contexts, the findings will improve the design and implementation of strategies to improve outcomes in young people, which will be relevant for achievement of global goals to eliminate HIV by 2030.
Reliability and responsiveness of the D12 and validity of its scores as a measure of dyspnoea severity in patients with rheumatoid arthritis-related interstitial lung disease
Authors: Swigris Jeffrey J , Danoff Sonye , Dellaripa Paul F , Doyle Tracy J , Solomon Joshua J 
Published: September 2023

BackgroundInterstitial lung disease due to rheumatoid arthritis (RA-ILD) affects a substantial minority of patients with RA, inducing life-altering symptoms, impairing quality of life (QOL) and forcing patients to confront the potential for shortened survival. Dyspnoea is the predominant respiratory symptom of RA-ILD and a strong driver of QOL impairment in patients with it. The D12 is a 12-item questionnaire that assesses the physical and affective components of dyspnoea. It was one of a battery of patient-reported outcomes used in the double-blind, placebo-controlled TRAIL 1 trial of pirfenidone for RA-ILD. There is little information on the reliability, validity or responsiveness of the D12 in RA-ILD.MethodsIn accordance with COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) methodology, we conducted analyses on data from the TRAIL 1 trial to assess the measurement properties of the D12.ResultsInternal consistency (α=0.95, 0.95, 0.95, 0.95 and 0.96 at baseline, 13, 26, 39 and 52 weeks) and test-retest reliability 0.85 (0.71 to 0.92) exceeded acceptability criteria. Well over the 75% benchmark of hypotheses (43/46=93%) around D12 measurement properties were confirmed. Known-groups validity was supported by significant differences between subgroups of patients with differing levels of dyspnoea (eg, St. George’s Respiratory Questionnaire (SGRQ) Activity score ≥50 vs <50, 9.36 (1.27) points, p<0.0001, with a large effect size=1.7) and physiological impairment at baseline. Longitudinal validity was supported by significant associations between D12 and anchor scores over time (eg, at 52 weeks, correlation between D12 change and SGRQ Activity change was 0.54, p<0.0001; between D12 change and Routine Assessment of Patient Index Data (RAPID) Functioning Component was 0.41, p<0.0001). A battery of analyses confirmed the responsiveness of D12 scores for capturing change in dyspnoea over time. We estimated the minimal within-patient change threshold for worsening as 3 points.ConclusionsD12 scores possess acceptable measurement properties in RA-ILD, such that it can be used with confidence in this population to assess dyspnoea severity defined by its physical and affective components. As validation is an ongoing process, and never accomplished in a single study, additional research on the psychometric properties of the D12 in RA-ILD is encouraged.
Perinatal and early life factors and asthma control among preschoolers: a population-based retrospective cohort study
Authors: Moore Linn E , Serrano-Lomelin Jesus , Rosychuk Rhonda J , Kozyrskyj Anita L , Chari Radha , Crawford Susan , Bakal Jeffery , Hicks Anne , Ducharme Francine M , Ospina Maria B 
Published: September 2023

BackgroundPreventing poor childhood asthma control is crucial for short-term and long-term respiratory health. This study evaluated associations between perinatal and early-life factors and early childhood asthma control.MethodsThis retrospective study used administrative health data from mothers and children born 2010–2012 with a diagnosis of asthma before age 5 years, in Alberta, Canada. The outcome was asthma control within 2 years after diagnosis. Associations between perinatal and early-life factors and risk of partly and uncontrolled asthma were evaluated by multinomial logistic regression.ResultsOf 7206 preschoolers with asthma, 52% had controlled, 37% partly controlled and 12% uncontrolled asthma 2 years after diagnosis. Compared with controlled asthma, prenatal antibiotics (adjusted risk ratio (aRR): 1.19; 95% CI 1.06 to 1.33) and smoking (aRR: 1.18; 95% CI 1.02 to 1.37), C-section delivery (aRR: 1.11; 95% CI 1.00 to 1.25), summer birth (aRR: 1.16; 95% CI 1.00 to 1.34) and early-life hospitalisation for respiratory illness (aRR: 2.24; 95% CI 1.81 to 2.76) increased the risk of partly controlled asthma. Gestational diabetes (aRR: 1.41; 95% CI 1.06 to 1.87), C-section delivery (aRR: 1.18; 95% CI 1.00 to 1.39), antibiotics (aRR: 1.32; 95% CI 1.08 to 1.61) and hospitalisation for early-life respiratory illness (aRR: 1.65; 95% CI 1.19 to 2.27) were associated with uncontrolled asthma.ConclusionMaternal perinatal and early-life factors including antibiotics in pregnancy and childhood, gestational diabetes, prenatal smoking, C-section and summertime birth, and hospitalisations for respiratory illness are associated with partly or uncontrolled childhood asthma. These results underline the significance of perinatal health and the lasting effects of early-life experiences on lung development and disease programming.
Point-of-care ultrasound-guided versus standard reduction of displaced distal radius fractures in the emergency department: a randomised controlled clinical trial
Authors: Haak Svenja L , Borgstede Marion G , Stolmeijer Renate , Bens Bas WJ , Boendermaker Annemieke E , van der Kolk Brigitta (Britt) YM , ter Maaten Jan C , ter Avest Ewoud , Lameijer Heleen 
Published: September 2023

BackgroundDuring closed reduction of displaced distal radius fractures, physical examination is used to determine the need for further manipulation before radiographic confirmation and cast application. Manipulation performed under ultrasound guidance has the potential to decrease the number of reduction attempts.MethodsThis multicentre randomised controlled trial was undertaken between December 2018 and July 2020 in the ED of four hospitals in the Netherlands. Patients aged ≥16 years presenting to the ED with a distal radius fracture requiring closed reduction were randomised to either point-of-care ultrasound (PoCUS)-guided or standard reduction. The primary outcome was the proportion of patients requiring more than one reduction attempt. The secondary outcomes were time to complete reduction and treatment plan at ED discharge (conservative or operative repair).ResultsA total of 214 patients were screened, of which 211 patients were included for primary endpoint analysis (87% female, median age 68 years, 94% dorsal angulation, 59% intra-articular and 73% multifragmentary). In total, 105 patients were randomised to standard treatment and 106 patients to PoCUS-guided fracture reduction. In the standard treatment group, 13 patients (12%) required more than one reduction attempt, compared with 6 patients (6%) in the PoCUS group (OR 2.35, 95% CI 0.86 to 6.45). The median reduction time was 5 min in the PoCUS group (IQR 3–6) vs 3 min (IQR 2–4) in the standard reduction group (p<0.001). At ED discharge, operative repair was indicated for 17 (16%) patients in the standard group and 21 (20%) patients in the PoCUS group (OR 0.78, 95% CI 0.39 to 1.58).ConclusionThis study could not demonstrate that PoCUS-guided reduction of distal radius fractures was associated with a statistically significant decrease in the number of reduction attempts.Trial registration numberThe Netherlands Trial Register (NTR7934).
Exercise in the workplace: examining the receptivity of practical and time-efficient stair-climbing “exercise snacks”
Authors: Stork Matthew J. , Marcotte-Chénard Alexis , Jung Mary E. , Little Jonathan P. 
Published: September 2023

In the workplace, people are often sedentary for prolonged time and do not regularly engage in physical activity—two factors independently linked to premature morbidity and mortality. This study aimed to determine the receptivity of incorporating practical stair-climbing “exercise snacks” (Snacks; three isolated bouts of ascending 53–60 stairs performed sporadically throughout the day) into workplace settings compared to more traditional high-intensity interval training (HIIT; performed as three bouts of 53-60 stairs within a structured HIIT workout) and to explore if these exercise strategies could influence sedentary and physical activity behaviour. Fourteen participants (12 women; Mage = 38.9 ± 10.2 years) completed two supervised exercise trials (Snacks and HIIT) followed by 1 week participating in either form of exercise in their workplace. Ratings of perceived exertion (RPE), affective valence, enjoyment, and self-efficacy were measured at the supervised exercise sessions. During the follow-up period, sedentary behaviour and physical activity were measured with an accelerometer. Affective valence was more positive ( p = 0.03; η2 p = 0.21) and there was a lower rise in RPE ( p = 0.01; η2 p = 0.29) during Snacks than HIIT. Post-exercise enjoyment of, and self-efficacy towards, Snacks and HIIT were high and similar ( ps > 0.05). After the supervised trials, 10/14 of the participants preferred Snacks and 4/14 preferred HIIT ( p = 0.18). On days when participants chose to perform either exercise modality, the average number of sit-to-stands in a 24 h period was increased (48.3 ± 8.7 to 52.8 ± 7.8; p = 0.03; Hedge's g = 0.73) and moderate-to-vigorous physical activity tended to increase (21.9 ± 18.2 to 38.1 ± 22.1 min; p = 0.06; Hedge's g = 0.60) compared to days when they chose not to exercise. Stair-climbing exercise snacks may be an attractive approach to implement in the workplace setting and has potential to positively impact sedentary behaviour and physical activity metrics.
Thermally stable reduced graphene oxide: An eco-friendly method for the synthesis of graphene compounds
Authors: Singh Pradeep Kumar , Kumar Singh Pankaj 
Published: September 2023

In this work, reduced graphene oxide (rGO) is generated by an environmentally friendly electrochemical technique using an aqueous solution of 2.5[Formula: see text]M nitric acid (HNO3), followed by thermal degradation at a temperature of 750∘C. To facilitate the exfoliation process, the electrolytic cell was equipped with a continuous supply of 54[Formula: see text]V DC. The microstructure of the rGO sheet has been analyzed using field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). The obtained results show that rGO sheets are irregularly stacked together, have a fractured surface, and porous structure. TGA analysis depicts that the total estimated weight loss was observed to be 40% because of the removal of the oxygen functionalities and volatile gases. X-Ray diffraction (XRD) analysis was used to analyze the phase purity, crystalline nature, interatomic distance as well as crystallite size of the rGO sheet. In the Raman study, the value [Formula: see text], which compares the peak intensity of the D band to intensity of the G band, provides evidence that the structural component associated with the rGO is present.
EZH2 Cooperates with BRD4-NUT to Drive NUT Carcinoma Growth by Silencing Key Tumor Suppressor Genes
Authors: Huang Yeying , Durall R. Taylor , Luong Nhi M. , Hertzler Hans J. , Huang Julianna , Gokhale Prafulla C. , Leeper Brittaney A. , Persky Nicole S. , Root David E. , Anekal Praju V. , Montero Llopis Paula D.L.M. , David Clement N. , Kutok Jeffery L. , Raimondi Alejandra , Saluja Karan , Luo Jia , Zahnow Cynthia A. , Adane Biniam , Stegmaier Kimberly , Hawkins Catherine E. , Ponne Christopher , Le Quan , Shapiro Geoffrey I. , Lemieux Madeleine E. , Eagen Kyle P. , French Christopher A. 
Published: September 2023

Abstract

NUT carcinoma is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of progrowth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NUT carcinoma that can impede BRD4-NUT's ability to activate genes, but the efficacy of BETi as monotherapy is limited. Here, we demonstrated that enhancer of zeste homolog 2 (EZH2), which silences genes through establishment of repressive chromatin, is a dependency in NUT carcinoma. Inhibition of EZH2 with the clinical compound tazemetostat potently blocked growth of NUT carcinoma cells. Epigenetic and transcriptomic analysis revealed that tazemetostat reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple tumor suppressor genes while having no effect on key oncogenic BRD4-NUT–regulated genes. Indeed, H3K27me3 and H3K27ac domains were found to be mutually exclusive in NUT carcinoma cells. CDKN2A was identified as the only gene among all tazemetostat-derepressed genes to confer resistance to tazemetostat in a CRISPR-Cas9 screen. Combined inhibition of EZH2 and BET synergized to downregulate cell proliferation genes, resulting in more pronounced growth arrest and differentiation than either inhibitor alone. In preclinical models, combined tazemetostat and BETi synergistically blocked tumor growth and prolonged survival of NUT carcinoma–xenografted mice, with complete remission without relapse in one cohort. Identification of EZH2 as a dependency in NUT carcinoma substantiates the reliance of NUT carcinoma tumor cells on epigenetic dysregulation of functionally opposite, yet highly complementary, chromatin regulatory pathways to maintain NUT carcinoma growth.

Significance:
Repression of tumor suppressor genes, including CDKN2A, by EZH2 provides a mechanistic rationale for combining EZH2 and BET inhibitors for the clinical treatment of NUT carcinoma.
See related commentary by Kazansky and Kentsis, p. 3827
Aplicativos de contact tracing na pandemia de covid-19 e os direitos humanos digitais em Portugal
Authors: Santos Niedja de Andrade e Silva Forte dos 
Published: September 2023

O artigo teve por objeto a análise jurídica da implementação dos aplicativos de contact tracing durante a pandemia de covid-19 em Portugal à luz da legislação em torno dos direitos humanos digitais vigente no país, inclusive a novel Carta Portuguesa de Direitos Humanos na Era Digital, em vigência desde julho de 2021. O principal método de pesquisa utilizado foi a revisão bibliográfica de artigos académicos indexados internacionalmente e a análise de conteúdo de instrumentos legislativos de Portugal e da União Europeia. Também incluiu a revisão bibliográfica de notícias sobre a pandemia e a covid-19 veiculadas sobretudo na Europa. Como um dos maiores desafios de saúde pública impostos à sociedade internacional na era corrente, o controle da disseminação da covid-19 demandou uma ampla gama de medidas. Entre estas, ganharam destaque os aplicativos de busca de comunicante. Alguns dos primeiros países a enfrentar a pandemia, sobretudo na Ásia, apontaram o papel fulcral de tais tecnologias na contenção da transmissão da enfermidade. Entretanto, a eficácia depende da adesão generalizada, somente realizável com o uso mandatório. Neste caso, além das críticas político-sociais relacionadas ao solucionismo tecnológico, emergem considerações relativas aos direitos fundamentais. Analisando o cenário português, semelhante ao de muitos outros países ocidentais, inclusive o Brasil, o artigo contribui com o debate acadêmico visando o uso da tecnologia não apenas durante a pandemia de covid-19, mas em futuros cenários de emergência sanitária, nomeadamente surtos, epidemias e pandemias a serem enfrentados pela humanidade.