bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormonal Receptor Immunochemistry Heterogeneity and 18F-FDG Metabolic Heterogeneity: Preliminary Results of Their Relationship and Prognostic Value in Luminal Non-Metastatic Breast Cancers
Authors: Aide Nicolas , Elie Nicolas , Blanc-Fournier Cécile , Levy Christelle , Salomon Thibault , Lasnon Charline 
Published: January 2021

IntroductionWe aimed to investigate whether 18F-FDG PET metabolic heterogeneity reflects the heterogeneity of estrogen receptor (ER) and progesterone receptor (PR) expressions within luminal non-metastatic breast tumors and if it could help in identifying patients with worst event-free survival (EFS).Materials and methodsOn 38 PET high-resolution breast bed positions, a single physician drew volumes of interest encompassing the breast tumors to extract SUVmax, histogram parameters and textural features. High-resolution immunochemistry (IHC) scans were analyzed to extract Haralick parameters and descriptors of the distribution shape. Correlation between IHC and PET parameters were explored using Spearman tests. Variables of interest to predict the EFS status at 8 years (EFS-8y) were sought by means of a random forest classification. EFS-8y analyses were then performed using univariable Kaplan-Meier analyses and Cox regression analysis. When appropriate, Mann-Whitney tests and Spearman correlations were used to explore the relationship between clinical data and tumoral PET heterogeneity variables.ResultsFor ER expression, correlations were mainly observed with 18F-FDG histogram parameters, whereas for PR expression correlations were mainly observed with gray-level co-occurrence matrix (GLCM) parameters. The strongest correlations were observed between skewness_ER and uniformity_HISTO (ρ = −0.386, p = 0.017) and correlation_PR and entropy_GLCM (ρ = 0.540, p = 0.001), respectively. The median follow-up was 6.5 years and the 8y-EFS was 71.0%. Random forest classification found age, clinical stage, SUVmax, skewness_ER, kurtosis_ER, entropy_HISTO, and uniformity_HISTO to be variables of importance to predict the 8y-EFS. Univariable Kaplan-Meier survival analyses showed that skewness_ER was a predictor of 8y-EFS (66.7 ± 27.2 versus 19.1 ± 15.2, p = 0.018 with a cut-off value set to 0.163) whereas other IHC and PET parameters were not. On multivariable analysis including age, clinical stage and skewness_ER, none of the parameters were independent predictors. Indeed, skewness_ER was significantly higher in youngest patients (ρ = −0.351, p = 0.031) and in clinical stage III tumors (p = 0.023).ConclusionA heterogeneous distribution of ER within the tumor in IHC appeared as an EFS-8y prognosticator in luminal non-metastatic breast cancers. Interestingly, it appeared to be correlated with PET histogram parameters which could therefore become potential non-invasive prognosticator tools, provided these results are confirmed by further larger and prospective studies.
Relevance of Neonatal Behavior Assessment Scale for Infants With Somatic Disorders: Comparison on One Matched Group of Control
Authors: Belot Rose-Angélique , Bouteloup Margaux , Mariage André , Candilis-huisman Drina , Mottet Nicolas , Mellier Denis 
Published: January 2021

Objective:To compare the Neonatal Behavior Assessment Scale results in two groups of infants with or without somatic disorder (N= 26).Method:The Neonatal Behavior Assessment Scale was administered to two groups (clinical and control) of 13 infants each, aged from 5 to 18 weeks, matched 2 by 2 according to sex, age, rank among siblings, and parental socio-professional category. The first group includes infants with somatic disorder (clinical) and is matched with a second group of “healthy infants” (control).Results:Results indicate that the mean score of the control group is significantly higher than that of the clinical group. Most of the items are affected by the presence of a somatic disorder. Indeed, five out of the six categories present a statistically significant difference in favor of the control group, more specifically for the items “state regulation,” “motor system,” and “orientation/interaction.”Conclusion:This exploratory research enables a precise description of infants' difficulty in regulating excitations and the impact of somatic disorders on their development. This innovative knowledge will assist pediatricians and health professionals in the understanding of infants' characteristics to develop an adapted-care.
Pediatric Liver Disease Patients and Secondary Glycosylation Abnormalities
Authors: Bogdańska Anna , Lipiński Patryk , Szymańska-Rożek Paulina , Jankowska Irena , Socha Piotr , Tylki-Szymańska Anna 
Published: January 2021

Background: Isoelectric focusing (IEF) of serum transferrin (Tf) is still the method of choice for diagnosis of congenital disorders of glycosylation (CDG). An abnormal glycosylation is also a known phenomenon in adult liver disease patients. The aim of this study was to characterize glycosylation disturbances in pediatric patients with primary liver disease. However, there are no reports of this phenomenon in children.Materials and Methods: Between 1995 and 2019, circa 2,000 serum Tf isoform analyses have been performed in children with primary liver diseases; some of them underwent subsequent analyses. We enrolled in this study 19 patients who developed an acute liver injury (ALI)/failure (ALF) or exhibited a chronic liver disease (CLD) and were evaluated and listed for liver transplantation (LTx) or had just undergone this procedure, and secondary abnormal serum Tf isoform profile.Results: Among 12 patients with ALI/ALF, 10 had an increased percentage of asialo-, monosialo-, and disialo-Tf isoforms. All patients with CLD had an increased percentage of asialo- and monosialo-Tf isoform. Two patients diagnosed with recurrent ALF had very specific serum Tf profile with a huge increase in the asialo- and monosialo-Tf isoform. On follow-up analyses (available in some patients), serum Tf IEF profile normalized in parallel to normalization of liver function tests, spontaneously or during treatment, including glucocorticosteroids in AIH, LTx in CLD.Conclusions: All pediatric patients with primary liver disease had increased asialo-Tf as well as monosialo-Tf isoforms. None of them had elevated percentage of trisialo-Tf isoform.
Artificial Intelligence in Pharmacoepidemiology: A Systematic Review. Part 2–Comparison of the Performance of Artificial Intelligence and Traditional Pharmacoepidemiological Techniques
Authors: Sessa Maurizio , Liang David , Khan Abdul Rauf , Kulahci Murat , Andersen Morten 
Published: January 2021

Aim: To summarize the evidence on the performance of artificial intelligence vs. traditional pharmacoepidemiological techniques.Methods: Ovid MEDLINE (01/1950 to 05/2019) was searched to identify observational studies, meta-analyses, and clinical trials using artificial intelligence techniques having a drug as the exposure or the outcome of the study. Only studies with an available full text in the English language were evaluated.Results: In all, 72 original articles and five reviews were identified via Ovid MEDLINE of which 19 (26.4%) compared the performance of artificial intelligence techniques with traditional pharmacoepidemiological methods. In total, 44 comparisons have been performed in articles that aimed at 1) predicting the needed dosage given the patient’s characteristics (31.8%), 2) predicting the clinical response following a pharmacological treatment (29.5%), 3) predicting the occurrence/severity of adverse drug reactions (20.5%), 4) predicting the propensity score (9.1%), 5) identifying subpopulation more at risk of drug inefficacy (4.5%), 6) predicting drug consumption (2.3%), and 7) predicting drug-induced lengths of stay in hospital (2.3%). In 22 out of 44 (50.0%) comparisons, artificial intelligence performed better than traditional pharmacoepidemiological techniques. Random forest (seven out of 11 comparisons; 63.6%) and artificial neural network (six out of 10 comparisons; 60.0%) were the techniques that in most of the comparisons outperformed traditional pharmacoepidemiological methods.Conclusion: Only a small fraction of articles compared the performance of artificial intelligence techniques with traditional pharmacoepidemiological methods and not all artificial intelligence techniques have been compared in a Pharmacoepidemiological setting. However, in 50% of comparisons, artificial intelligence performed better than pharmacoepidemiological techniques.
Methylene Blue Inhibits the SARS-CoV-2 Spike–ACE2 Protein-Protein Interaction–a Mechanism that can Contribute to its Antiviral Activity Against COVID-19
Authors: Bojadzic Damir , Alcazar Oscar , Buchwald Peter 
Published: January 2021

Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its cognate receptor ACE2, which is the first critical step initiating the viral attachment and entry of this coronavirus responsible for the ongoing COVID-19 pandemic. As part of this, we found that methylene blue, a tricyclic phenothiazine compound approved by the FDA for the treatment of methemoglobinemia and used for other medical applications (including the inactivation of viruses in blood products prior to transfusion when activated by light), inhibits this interaction. We confirmed that it does so in a concentration-dependent manner with a low micromolar half-maximal inhibitory concentration (IC50 = 3 μM) in our protein-based ELISA-type setup, while chloroquine, siramesine, and suramin showed no inhibitory activity in this assay. Erythrosine B, which we have shown before to be a promiscuous SMI of PPIs, also inhibited this interaction. Methylene blue inhibited the entry of a SARS-CoV-2 spike bearing pseudovirus into ACE2-expressing cells with similar IC50 (3.5 μM). Hence, this PPI inhibitory activity could contribute to its antiviral activity against SARS-CoV-2 even in the absence of light by blocking its attachment to ACE2-expressing cells and making this inexpensive and widely available drug potentially useful in the prevention and treatment of COVID-19 as an oral or inhaled medication.
Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage
Authors: Dornellas Ana Paula S. , Macedo Giovana C. , McFarland Minna H. , Gómez-A Alexander , O’Buckley Todd K. , Da Cunha Claudio , Morrow A. Leslie , Robinson Donita L. 
Published: January 2021

Mesolimbic dopamine transmission is dysregulated in multiple psychiatric disorders, including addiction. Previous studies found that the endogenous GABAergic steroid (3α,5α)-3-hydroxy-5-pregnan-20-one (allopregnanolone) modulates dopamine levels in the nucleus accumbens and prefrontal cortex. As allopregnanolone is a potent positive allosteric modulator of GABAA receptors, and GABAA receptors can regulate dopamine release, we hypothesized that allopregnanolone would reduce phasic fluctuations in mesolimbic dopamine release that are important in learning and reward processing. We used fast-scan cyclic voltammetry in anesthetized female and male rats to measure dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area, before and after administration of allopregnanolone. Allopregnanolone (7.5–25 mg/kg, IP) reduced evoked dopamine release in both male and female rats, compared to β-cyclodextrin vehicle. In males, all doses of allopregnanolone decreased dopamine transmission, with stronger effects at 15 and 25 mg/kg allopregnanolone. In females, 15 and 25 mg/kg allopregnanolone reduced dopamine release, while 7.5 mg/kg allopregnanolone was no different from vehicle. Since allopregnanolone is derived from progesterone, we hypothesized that high endogenous progesterone levels would result in lower sensitivity to allopregnanolone. Consistent with this, females in proestrus (high progesterone levels) were less responsive to allopregnanolone than females in other estrous cycle stages. Furthermore, 30 mg/kg progesterone reduced evoked dopamine release in males, similar to allopregnanolone. Our findings confirm that allopregnanolone reduces evoked dopamine release in both male and female rats. Moreover, sex and the estrous cycle modulated this effect of allopregnanolone. These results extend our knowledge about the pharmacological effects of neurosteroids on dopamine transmission, which may contribute to their therapeutic effects.
Montelukast Use Decreases Cardiovascular Events in Asthmatics
Authors: Hoxha Malvina , Tedesco Calogero C. , Quaglin Silvana , Malaj Visar , Pustina Linda , Capra Valerie , Evans Jilly F. , Sala Angelo , Rovati G. Enrico 
Published: January 2021

Cysteinyl leukotrienes are proinflammatory mediators with a clinically established role in asthma and a human genetic and preclinical role in cardiovascular pathology. Given that cardiovascular disease has a critical inflammatory component, the aim of this work was to conduct an observational study to verify whether the use of a cysteinyl leukotriene antagonist, namely, montelukast, may protect asthmatic patients from a major cardiovascular event and, therefore, represent an innovative adjunct therapy to target an inflammatory component in cardiovascular disease. We performed an observational retrospective 3-year study on eight hundred adult asthmatic patients 18 years or older in Albania, equally distributed into two cohorts, exposed or nonexposed to montelukast usage, matched by age and gender according to information reported in the data collection. Patients with a previous history of myocardial infarction or ischemic stroke were excluded. In summary, 37 (4.6%) of the asthmatic patients, 32 nonexposed, and five exposed to montelukast suffered a major cardiovascular event during the 3-year observation period. All the cardiovascular events, in either group, occurred among patients with an increased cardiovascular risk. Our analyses demonstrate that, independent from gender, exposure to montelukast remained a significant protective factor for incident ischemic events (78% or 76% risk reduction depending on type of analysis). The event-free Kaplan–Meier survival curves confirmed the lower cardiovascular event incidence in patients exposed to montelukast. Our data suggest that there is a potential preventative role of montelukast for incident cardiac ischemic events in the older asthmatic population, indicating a comorbidity benefit of montelukast usage in asthmatics by targeting cysteinyl leukotriene-driven cardiac disease inflammation.
ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts
Authors: Yang Xiaolan , Xiao Yongqiang , Zhong Chenjian , Shu Futing , Xiao Shichu , Zheng Yongjun , Xia Zhaofan 
Published: January 2021

Background:Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great antitumor characteristics by targeting tumor cell apoptosis. The objective of this study was to explore whether ABT-263 could target apoptosis of overactivated myofibroblasts in hypertrophic scar.Methods:In vivo, we used ABT-263 to treat scars in a rabbit ear scar model. Photographs and ultrasound examination were taken weekly, and scars were harvested on day 42 for further Masson trichrome staining.In vitro, the expression levels of BCL-2 family members, including prosurvival proteins, activators, and effectors, were detected systematically in hypertrophic scar tissues and adjacent normal skin tissues, as well as in human hypertrophic scar fibroblasts (HSFs) and human normal dermal fibroblasts (HFBs). The roles of ABT-263 in apoptosis and proliferation of HSFs and HFBs were determined by annexin V/PI assay, CCK-8 kit, and cell cycle analysis. Mitochondrial membrane potential was evaluated by JC-1 staining and the expression of type I/III collagen and α-SMA was measured by PCR, western blotting, and immunofluorescence staining. Furthermore, immunoprecipitation was performed to explore the potential mechanism.Results:In vivo, ABT-263 could significantly improve the scar appearance and collagen arrangement, decrease scar elevation index (SEI), and induce cell apoptosis.In vitro, the expression levels of BCL-2, BCL-XL, and BIM were significantly higher in scar tissues and HSFs than those in normal skin tissues and HFBs. ABT-263 selectively induced HSFs apoptosis by releasing BIM from binding with prosurvival proteins. Moreover, ABT-263 inhibited HSFs proliferation and reduced the expression of α-SMA and type I/III collagen in a concentration- and time- dependent manner.Conclusion:HSFs showed increased mitochondrial priming with higher level of proapoptotic activator BIM and were primed to death. ABT-263 showed great therapeutic ability in the treatment of hypertrophic scar by targeting HSFs.
Ischemic and Bleeding Events of Ticagrelor Monotherapy in Korean Patients With and Without Diabetes Mellitus: Insights From the TICO Trial
Authors: Yun Kyeong Ho , Cho Jae Young , Lee Seung Yul , Rhee Sang Jae , Kim Byeong Keuk , Hong Myeong Ki , Jang Yangsoo , Oh Seok Kyu ,   the TICO Investigators
Published: January 2021

Background: Ticagrelor monotherapy after 3 months dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, the impact of this approach among the patient with diabetes remains unknown.Methods: This was a sub-analysis of the Ticagrelor Monotherapy after 3 months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial. After successful PCI, the patients were randomly assigned to ticagrelor monotherapy after 3-months DPAT or to ticagrelor-based 12-months DAPT. We compared ischemic events and bleeding events between the patients with diabetes and without diabetes for 12 months. Ischemic events were defined as death, myocardial infarction, ischemic stroke, transient ischemic attack, stent thrombosis, and any revascularizations. Bleeding events were defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria and Bleeding Academic Research Consortium (BARC) definition.Results: Between August 2015 and October 2018, 3,056 patients were enrolled in the TICO trial, of which 835 (27.3%) had diabetes mellitus. Diabetes mellitus was associated with all evaluated ischemic and bleeding events. No significant differences in any ischemic events were observed in patients with diabetes between ticagrelor monotherapy after 3-months DAPT and ticagrelor-based 12-months DAPT (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.45–1.52, p = 0.540). In patients with diabetes, the overall incidence of bleeding complications during the 12-months follow-up period did not differ between the two treatment groups (HR 0.83, 95% CI 1.48–1.43, p = 0.505). However, ticagrelor monotherapy was significantly reduced both any TIMI bleeding and BARC three or five bleeding events in diabetes patients in the 3-months landmark analysis, after 3-months DAPT period (HR 0.20, 95% CI 0.07–0.59, p = 0.003).Conclusion: In diabetic patients, ticagrelor monotherapy showed a lower incidence of bleeding complications after 3-months DAPT period, without increasing ischemic complications, compared with ticagrelor-based 12-months DAPT (ClinicalTrials.gov Identifier: NCT02494895).
Students’ Motivation and Affection Profiles and Their Relation to Mathematics Achievement, Persistence, and Behaviors
Authors: Xiao Feiya , Sun Li 
Published: January 2021

ObjectiveWe aimed to explore profiles of subgroups of United States students based on their motivational and affective characteristics and investigate the differences in math-related behaviors, persistence, and math achievement across profiles.MethodWe used 1,464 United States students (male 743 51%, female 721 49%, age 15.82 ± 0.28) from PISA 2012 United States data in our study. First, we employed latent profile analysis and secondary clustering to identify subgroups of students based on motivational (math self-concept, interest in math, perceived control, and instrumental motivation) and affective factors (math anxiety). Next, we used regression to compare differences in math behavior, persistence, and achievement among all identified subgroups.ResultsWe found five distinct groups of students with different patterns of motivation and affection. The subgroup of students with the lowest math anxiety and the highest motivation levels showed the highest math achievement and levels of persistence. The groups with high math interest, math self-concept, and instrumental motivation showed the most frequent math-related behaviors.ConclusionsOur findings reveal the complexity of the students’ motivational and affective profiles. Our findings are significant for teachers and educators to understand the diversity of students and provide theoretical and practical support for individualized and differentiated instruction.
Bifidobacterium animalis subsp. lactis BB-12 Improves the State Anxiety and Sports Performance of Young Divers Under Stress Situations: A Single-Arm, Prospective Proof-of-Concept Study
Authors: Dong Weizhong , Wang Ying , Liao Shuaixiong , Tang Wei , Peng Li , Song Gang 
Published: January 2021

BackgroundAthletes will increase their state anxiety under stress situations, which will lead to the decline of sports performance. The improvement of anxiety by probiotics has been reported, but there is a lack of research in the athlete population. The purpose of the current study is to explore the effectiveness of probiotics in improving athletes’ state anxiety and sports performance under stress situations.MethodsWe conducted this single-arm study in Chongqing Institute of Sports Technology. In the 8-week study, 21 Chongqing young divers (mean age: 9.10 ± 1.80) were given probiotic Bifidobacterium animalis subsp. lactis BB-12 (1 × 109 colony-forming units/100 g) daily. The state anxiety and sports performance of athletes were measured before, during, and after the intervention, and the gut microbiota of athletes was measured before and after the intervention.ResultsThe intervention results showed that cognitive state anxiety, somatic state anxiety, and anxiety emotion were improved (cognitive: Z = −3.964, P &lt; 0.001; somatic: Z = −3.079, P = 0.003; anxiety: Z = −2.973, P &lt; 0.001). In terms of gut microbiota, the intervention did not change the gut microbial composition (such as α diversity and β diversity) but increased the abundance of Bifidobacteriaceae. At the 8th week, the performance of athletes under stress was significantly improved (χ2 = 7.88, P = 0.019).LimitationsFirst of all, due to the restriction of the number of subjects in this study, there was no control group. Secondly, although the athletes’ diet was recorded in this study, the influence of this factor on gut microbiota was not eliminated. Finally, the anxiety level of the athletes in this study was obtained through a self-report, lacking physiological data in state anxiety.ConclusionThe results show that probiotics intervention can improve the state anxiety of athletes under stress situation and improve the performance of athletes under stress situation.