bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized follow-up of circulating DNA in resected stage III/IV melanoma: PERCIMEL multicentric prospective study protocol
Authors: Geoffrois Lionnel , Harlé Alexandre , Sahki Nassim , Sikanja Aleksandra , Granel-Brocard Florence , Hervieu Alice , Mortier Laurent , Jeudy Géraldine , Michel Catherine , Nardin Charlée , Huin-Schohn Cécile , Merlin Jean-Louis 
Published: June 2023

Abstract
Background
With more than 15,000 new cases /year in France and 2,000 deaths, cutaneous melanoma represents approximately 4% of incidental cancers and 1.2% of cancer related deaths. In locally advanced (stage III) or resectable metastatic (stage IV) melanomas, medical adjuvant treatment is proposed and recent advances had shown the benefit of anti-PD1/PDL1 and anti-CTLA4 immunotherapy as well as anti-BRAF and anti-MEK targeted therapy in BRAF V600 mutated tumors. However, the recurence rate at one year is approximately 30% and justify extensive research of predictive biomarkers. If in metastatic disease, the follow-up of circulating tumor DNA (ctDNA) has been demonstrated, its interest in adjuvant setting remains to be precised, especially because of a lower detection rate. Further, the definition of a molecular response could prove useful to personalized treatment.

Methods
PERCIMEL is an open prospective multicentric study executed through collaboration of the Institut de Cancérologie de Lorraine (non-profit comprehensive cancer center) and 6 French university and community hospitals. A total of 165 patients with resected stage III and IV melanoma, eligible to adjuvant imunotherapy or anti-BRAF/MEK kinase inhibitors will be included. The primary endpoint is the presence of ctDNA, 2 to 3 weeks after surgery, defined as mutated ctDNA copy number calculated as the allelic fraction of a clonal mutation relative to total ctDNA. Secondary endpoints are recurrence-free survival, distant metastasis-free survival and specific survival. We will follow ctDNA along treatment, quantitatively through ctDNA mutated copy number variation, qualitatively through the presence of cfDNA and its clonal evolution. Relative and absolute variations of ctDNA during follow-up will be also analyzed.
PERCIMEL study aims at provide scientific evidence that ctDNA quantitative and qualitative variations can be used to predict the recurrence of patients with melanoma treated with adjuvant immunotherapy or kinase inhibitors, thus defining the notion of molecular recurrence.
Effect of alirocumab on cataracts in patients with acute coronary syndromes
Authors: Suc Gaspard , Schwartz Gregory G. , Goodman Shaun G. , Jukema J. Wouter , Manvelian Garen , Poulouin Yann , Pordy Robert , Scemama Michel , Szarek Michael , Steg Ph. Gabriel ,   ODYSSEY OUTCOMES Investigators
Published: June 2023

Abstract
Background
Some data suggest that low levels of low-density lipoprotein cholesterol (LDL-C) are associated with risk of cataracts. Proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors reduce LDL-C below levels achieved with statins alone. We determined whether the incidence of cataracts was influenced by treatment with the PCSK9 inhibitor alirocumab versus placebo, and whether that incidence was affected by achieved LDL-C levels.

Methods
The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome receiving high-intensity or maximum-tolerated statin. Incident cataracts were pre-specified events of interest. In multivariable analysis using propensity score-matching on characteristics including cataract risk factors, incident cataracts were compared in the alirocumab and placebo groups according to LDL-C levels achieved with alirocumab.

Results
Over median follow-up of 2.8 years (interquartile range 2.3 − 3.4), the incidence of cataracts was similar with alirocumab (127/9462 [1.3%]) versus placebo (134/9462 [1.4%]); hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74 − 1.20). In patients treated with alirocumab with ≥ 2 LDL-C values < 25 mg/dL (0.65 mmol/L), the incidence of cataracts was 71/4305 (1.6%), versus 60/4305 (1.4%) in propensity score-matched patients from the placebo group (HR 1.10, CI 95% 0.78 − 1.55). In patients treated with alirocumab with ≥ 2 LDL-C values < 15 mg/dL (0.39 mmol/L), the incidence of cataracts was 13/782 (1.7%), versus 36/2346 (1.5%) in matched patients from the placebo group (HR 1.03, CI 95% 0.54 − 1.94).

Conclusion
Treatment with alirocumab versus placebo, added to statin, did not influence the incidence of cataracts, even when achieved LDL-C levels on alirocumab were very low. Longer follow-up studies might be necessary to exclude the long-term effects on the incidence or progression of cataracts.

Trial registration
ClinicalTrials.gov Identifier: NCT01663402.
Prevalence and risk factors of prehypertension/hypertension among freshman students from the Vietnam National University: a cross-sectional study
Authors: Vo Hong-Khoi , Nguyen Dung Viet , Vu Thom Thi , Tran Hieu Ba , Nguyen Hoai Thi Thu 
Published: June 2023

Abstract
Background
Prehypertension (PHT) and hypertension (HTN) in young adults are essential risk factors for other cardiovascular diseases (CVD) in later years of life. However, there is a lack of knowledge about the burden and risk factors of PHT/HTN for Vietnamese youth. The aim of this study was to investigate the prevalence of PHT/HTN and risk factors among university students in Hanoi, Vietnam.

Methods
This study was designed as a cross-sectional investigation with 840 students (394 males and 446 females) randomly sampled from freshmen of Vietnam National University, Hanoi (VNU). Socio-demographic, anthropometric, and lifestyle data were collected using questionnaire forms and physical measurements. HTN was defined as blood pressure (BP) ≥ 140/90 mmHg and/or current treatment with antihypertensive medications. PHT was defined as a systolic BP from 120 to 139 mmHg and/or a diastolic BP from 80 to 89 mmHg. Body mass index (BMI) was classified according to the WHO diagnostic criteria for Asian adults: normal weight (BMI 18.5–22.9 kg/m2), underweight (BMI < 18.5 kg/m2), overweight (BMI 23–24.9 kg/m2), and obese (BMI ≥ 25 kg/m2). Bivariable and multivariable log-binomial regression analyses were conducted to explore the association of PHT/HTN with different risk factors.

Results
The overall prevalence of prehypertension and hypertension was 33.5% [95% CI: 30.3–36.8%] (54.1% in men and 15.3% in women) and 1.4% [95% CI: 0.7–2.5%] (2.5% in men and 0.5% in women), respectively. Regarding CVD major risk factors, 119 (14.2%) were identified as overweight/obese, 461 (54.9%) were physical inactivity, 29.4% of men and 8.1% of women reported consuming alcohol. The multivariable analysis indicated the male sex (adjusted prevalence ratio [aPR] = 3.07; 95% CI: 2.32–4.06), alcohol consumption (aPR = 1.28; 95% CI: 1.03–1.59) and obesity (aPR = 1.35; 95% CI: 1.08–1.68) as the independent risk factors for PHT/HTN.

Conclusions
The results revealed the high burden of prehypertension and hypertension among university freshmen in VNU. Male sex, alcohol consumption, and obesity were identified as important risk factors for PHT/HTN. Our study suggests an early screening program for PHT/HTN and campaigns to promote a healthy lifestyle for young adults in Vietnam.
The effect of carbodiimide on push-out bond strength of fiber posts and endogenous enzymatic activity
Authors: Josic Uros , Mazzitelli Claudia , Maravic Tatjana , Comba Allegra , Cadenaro Milena , Radovic Ivana , Sebold Maicon , Turco Gianluca , Breschi Lorenzo , Mazzoni Annalisa 
Published: June 2023

Abstract
Background
To investigate the effect of 0.3 M 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC) aqueous solution pretreatment on push-out bond strength (PBS) and matrix-metalloproteinases (MMPs) activity within radicular dentin when different post cementation strategies were employed.

Methods
One hundred and twenty monoradicular human teeth were endodontically treated and randomly divided into six groups, depending on the cementation strategy and root dentin pretreatment (n = 20): EAR: cementation with an etch-and-rinse adhesive (LuxaBond Total Etch, DMG) and resin cement (LuxaCore Z Dual, DMG); EAR/EDC: 1 min EDC pretreatment after etching + EAR; SE: cementation with a self-etch primer (Multilink Primer, Ivoclar Vivadent) and corresponding cement (Multilink Automix, Ivoclar Vivadent); SE/EDC: self-etch primer + EDC pretreatment + SE; SA: cementation with a universal self-adhesive cement (RelyX Universal, 3 M); SA/EDC: EDC pretreatment + SA. Slices were submitted to PBS test and interfacial nanoleakage evaluation 24 h after cementation or after thermocycling (40.000 cycles, 5–55 °C). To investigate the effect of EDC on MMPs activity, 4 additional first maxillary premolars per group were processed for in situ zymography analysis. Multivariate ANOVA and post hoc Tukey tests were used to analyze PBS values. The data from in situ zymography were analyzed with Kruskal-Wallis test and Dunn’s pairwise multiple comparison procedures (α = 0.05).

Results
The variables “EDC pretreatment”, “root region” and “thermocycling” significantly influenced PBS (p < 0.05), while the variable “cementation strategy” had no influence (p > 0.05). Thermocycling significantly reduced PBS in SE and SA groups (p < 0.05). EDC was effective in preserving PBS after artificial aging. EDC pretreatment significantly reduced enzymatic activity at baseline in EAR and SE groups, and in SA group after thermocycling (p < 0.05).

Conclusions
The use of EDC prevents the reduction of bond-strength values after artificial aging and silences endogenous enzymatic activity within radicular dentin when different cementation strategies were employed.
Identification of candidate metabolite biomarkers for metabolic syndrome and its five components in population-based human cohorts
Authors: Shi Mengya , Han Siyu , Klier Kristin , Fobo Gisela , Montrone Corinna , Yu Shixiang , Harada Makoto , Henning Ann-Kristin , Friedrich Nele , Bahls Martin , Dörr Marcus , Nauck Matthias , Völzke Henry , Homuth Georg , Grabe Hans J. , Prehn Cornelia , Adamski Jerzy , Suhre Karsten , Rathmann Wolfgang , Ruepp Andreas , Hertel Johannes , Peters Annette , Wang-Sattler Rui 
Published: June 2023

Abstract
Background
Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its associated risk factors to better understand the complex interplay of underlying signaling pathways.

Methods
We quantified serum samples of the KORA F4 study participants (N = 2815) and analyzed 121 metabolites. Multiple regression models adjusted for clinical and lifestyle covariates were used to identify metabolites that were Bonferroni significantly associated with MetS. These findings were replicated in the SHIP-TREND-0 study (N = 988) and further analyzed for the association of replicated metabolites with the five components of MetS. Database-driven networks of the identified metabolites and their interacting enzymes were also constructed.

Results
We identified and replicated 56 MetS-specific metabolites: 13 were positively associated (e.g., Val, Leu/Ile, Phe, and Tyr), and 43 were negatively associated (e.g., Gly, Ser, and 40 lipids). Moreover, the majority (89%) and minority (23%) of MetS-specific metabolites were associated with low HDL-C and hypertension, respectively. One lipid, lysoPC a C18:2, was negatively associated with MetS and all of its five components, indicating that individuals with MetS and each of the risk factors had lower concentrations of lysoPC a C18:2 compared to corresponding controls. Our metabolic networks elucidated these observations by revealing impaired catabolism of branched-chain and aromatic amino acids, as well as accelerated Gly catabolism.

Conclusion
Our identified candidate metabolite biomarkers are associated with the pathophysiology of MetS and its risk factors. They could facilitate the development of therapeutic strategies to prevent type 2 diabetes and cardiovascular disease. For instance, elevated levels of lysoPC a C18:2 may protect MetS and its five risk components. More in-depth studies are necessary to determine the mechanism of key metabolites in the MetS pathophysiology.
Helicobacter pylori promotes gastric intestinal metaplasia through activation of IRF3-mediated kynurenine pathway
Authors: Liang Xinhua , Du Wenjun , Huang Ling , Xiang Li , Pan Wenxu , Yang Fangying , Zheng Fengfeng , Xie Yongwu , Geng Lanlan , Gong Sitang , Xu Wanfu 
Published: June 2023

Abstract
Background
Metabolic reprogramming is a critical event for cell fate and function, making it an attractive target for clinical therapy. The function of metabolic reprogramming in Helicobacter pylori (H. pylori)-infected gastric intestinal metaplasia remained to be identified.

Methods
Xanthurenic acid (XA) was measured in gastric cancer cells treated with H. pylori or H. pylori virulence factor, respectively, and qPCR and WB were performed to detect CDX2 and key metabolic enzymes expression. A subcellular fractionation approach, luciferase and ChIP combined with immunofluorescence were applied to reveal the mechanism underlying H. pylori mediated kynurenine pathway in intestinal metaplasia in vivo and in vitro.

Results
Herein, we, for the first time, demonstrated that H. pylori contributed to gastric intestinal metaplasia characterized by enhanced Caudal-related homeobox transcription factor-2 (CDX2) and mucin2 (MUC2) expression, which was attributed to activation of kynurenine pathway. H. pylori promoted kynurenine aminotransferase II (KAT2)-mediated kynurenine pathway of tryptophan metabolism, leading to XA production, which further induced CDX2 expression in gastric epithelial cells. Mechanically, H. pylori activated cyclic guanylate adenylate synthase (cGAS)-interferon regulatory factor 3 (IRF3) pathway in gastric epithelial cells, leading to enhance IRF3 nuclear translocation and the binding of IRF3 to KAT2 promoter. Inhibition of KAT2 could significantly reverse the effect of H. pylori on CDX2 expression. Also, the rescue phenomenon was observed in gastric epithelial cells treated with H. pylori after IRF3 inhibition in vitro and in vivo. Most importantly, phospho-IRF3 was confirmed to be a clinical positive relationship with CDX2.

Conclusion
These finding suggested H. pylori contributed to gastric intestinal metaplasia through KAT2-mediated kynurenine pathway of tryptophan metabolism via cGAS-IRF3 signaling, targeting the kynurenine pathway could be a promising strategy to prevent gastric intestinal metaplasia caused by H. pylori infection.
The impact of the Safe Delivery Application on knowledge and skills managing postpartum haemorrhage in a low resource setting: a cluster randomized controlled trial in West Wollega region, Ethiopia
Authors: Christiansen Ann-Marie Hellerung , Sørensen Bjarke Lund , Boas Ida Marie , Bedesa Tariku , Fekede Wondewossen , Nielsen Henriette Svarre , Lund Stine 
Published: June 2023

Abstract
Background
Postpartum haemorrhage is one of the leading causes of maternal mortality in low-income countries. Improving health workers' competencies in obstetric emergencies in low-income settings, has been recognized as an important factor in preventing maternal mortality and morbidity. mHealth interventions in maternal and newborn health care has shown the potential to improve health service delivery. Strong study designs such as randomized controlled trials are missing to estimate the effectiveness of the mHealth interventions.

Methods
Between August 2013 and August 2014, 70 health facilities in West Wollega Region, Ethiopia were included and randomized to intervention or control in a cluster randomized controlled trial. At intervention facilities birth attendants were provided with a smartphone with the SDA installed. Of 176 midwives and “health extension workers,” 130 completed at 12 months follow-up. At baseline and after 6- and 12-months participants were assessed. Knowledge was tested by a Key Feature Questionnaire, skills by an Objective Structured Assessment of Technical Skills in a structured role-play scenario.

Results
Baseline skills scores were low and comparable with a median of 12/100 in the intervention and the control group. After 6 months skills had doubled in the intervention group (adjusted mean difference 29.6; 95% CI 24.2–35.1 compared to 1·8; 95% CI – 2.7 to 6.3 in the control group). At 12 months skills had further improved in the intervention group (adjusted mean difference 13.3; 95% CI 8.3–18.3 compared to 3.1; 95% CI – 1.0 to 7.3 in the control group). Knowledge scores also significantly improved in the intervention group compared to the control (adjusted mean difference after 12 months 8.5; 95% CI 2.0–15.0).

Conclusion
The Safe Delivery App more than doubled clinical skills for managing postpartum haemorrhage among birth attendants making it an attractive tool to reduce maternal mortality.
Trial registration: Clinicaltrial.gov Identifier NCT01945931. September 5, 2013.
Prevalence of malnutrition & anemia in preschool children; a single center study
Authors: Fouad Hanan Mina , Yousef Aly , Afifi Ahmed , Ghandour Ahmed A. , Elshahawy Amira , Elkhawass Ayman , Hawees Hazem , Shaheen Eman , Alaaeldin Mohamed , Kamal Mostafa , Bastawy Samah , Rabie Samah , Wissa Farah , Shalaby Sherine 
Published: June 2023

Abstract
Background
Malnutrition including undernutrition, overnutrition, and micronutrient deficiencies are considerable problems worldwide, with variable burdens among different communities. Its complications include physical and cognitive impairment, with the probability of irreversible lifelong consequences. We aimed to assess the prevalence of undernutrition, overweight, obesity, and anemia in preschoolers, being a risk group for developmental adverse events.

Methods
We recruited 505 healthy preschool children, with a male: female ratio of 1.05:1. Children with chronic diseases were excluded. We used anthropometry and complete blood count to screen for malnutrition and anemia.

Results
The mean age of the study group was 3.8 ± 1.4 years (1.02–7). The screening results were average in 228 (45.1%) children, while 277 (54.9%) children had either abnormal anthropometry, anemia, or both. We observed undernutrition in 48 (9.5%) children; among them, 33 (6.6%) were underweight, 33 (6.6%) wasted, and 15 (3%) were stunted, with no significant difference between children aged below or above five. We identified overnutrition in 125 (24.8%); 43 (8.5%) were overweight, 12 (2.4%) were obese, and 70 (13.9%) had a high body mass index Z score, not qualifying the definition of overweight. Anemia was diagnosed in 141 (27.9%) children and was significantly more frequent among older children without gender discrimination. About 10% (50 children) had both anemia and abnormal anthropometry. The frequency of abnormal anthropometry was comparable between children with anemia and those with normal hemoglobin.

Conclusion
Malnutrition and anemia in preschoolers are still a heavy burden affecting about half of our study group, with an upward trend towards the overnutrition side. Anemia is still a moderate public health problem in preschoolers.
Feedback circuits are numerous in embryonic gene regulatory networks and offer a stabilizing influence on evolution of those networks
Authors: Massri Abdull Jesus , McDonald Brennan , Wray Gregory A. , McClay David R. 
Published: June 2023

AbstractThe developmental gene regulatory networks (dGRNs) of two sea urchin species, Lytechinus variegatus (Lv) and Strongylocentrotus purpuratus (Sp), have remained remarkably similar despite about 50 million years since a common ancestor. Hundreds of parallel experimental perturbations of transcription factors with similar outcomes support this conclusion. A recent scRNA-seq analysis suggested that the earliest expression of several genes within the dGRNs differs between Lv and Sp. Here, we present a careful reanalysis of the dGRNs in these two species, paying close attention to timing of first expression. We find that initial expression of genes critical for cell fate specification occurs during several compressed time periods in both species. Previously unrecognized feedback circuits are inferred from the temporally corrected dGRNs. Although many of these feedbacks differ in location within the respective GRNs, the overall number is similar between species. We identify several prominent differences in timing of first expression for key developmental regulatory genes; comparison with a third species indicates that these heterochronies likely originated in an unbiased manner with respect to embryonic cell lineage and evolutionary branch. Together, these results suggest that interactions can evolve even within highly conserved dGRNs and that feedback circuits may buffer the effects of heterochronies in the expression of key regulatory genes.
Ground strains induced by the 2022 Hunga-Tonga volcanic eruption, observed by a 1500-m laser strainmeter at Kamioka, Japan
Authors: Takamori Akiteru , Araya Akito , Miyo Kouseki , Washimi Tatsuki , Yokozawa Takaaki , Hayakawa Hideaki , Ohashi Masatake 
Published: June 2023

AbstractIn this study, we detected the horizontal ground strains induced by the atmospheric Lamb wave emitted from the 2022 eruption of the Tonga–Hunga Ha’apai undersea volcano, at an underground observatory in Kamioka, Japan. The observed strains were in the range of $${10}^{-11}$$

10

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11

–$${10}^{-10}$$

10

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10

and were measured precisely using a 1500-m laser strainmeter with a high resolution in the order of $${10}^{-12}$$

10

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12

. This was one of the first observations of a Lamb wave using a laser strainmeter. The strainmeter was constructed in a tunnel of the KAGRA gravitational-wave telescope. Our observations demonstrate that strain and atmospheric pressure were clearly correlated, resulting in a regression coefficient of $$- \left(2.3-3.7\right)\times {10}^{-10}$$

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2.3
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3.7

×

10

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10

strain/hPa. This finding was compared with the responses under regular pressure conditions and the estimations obtained using the local deformation and traveling wave models. The observed coefficients for the Lamb wave exhibited smaller magnitudes than those observed under regular conditions and take values between that of the two theoretical models. These results reflect the intermediate scale of the pressure distribution of the Lamb wave between the assumptions of the simple models. The strain variations were also found to have started earlier than the corresponding pressure changes at the observation site with characteristic time lags ranging from 25 to 155 s. In addition, several aspects related to the mechanism that created the time lags are discussed.
Graphical Abstract
Dynamics of squirmers in explicitly modeled polymeric fluids
Authors: Zöttl Andreas 
Published: June 2023

Abstract
Biological microswimmers such as bacteria and sperm cells often encounter complex biological fluid environments. Here we use the well-known squirmer microswimmer model to show the importance of the local fluid microstructure and non-continuum effects on their swimming speed in different polymeric and filamentous fluids. Surprisingly, we find that different squirmer types move at considerably different speed in filamentous fluids which cannot be explained by existing continuum models, but by considering the local fluid and polymer properties around the squirmers. Furthermore, direct squirmer-polymer interactions slow down in particular pushers by trapping large stiff filaments in a self-generated recirculation region in front of them.