bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperphagia and impulsivity: use of self-administered Dykens’ and in-house impulsivity questionnaires to characterize eating behaviors in children with severe and early-onset obesity
Authors: Arnouk Lara , Chantereau Hélène , Courbage Sophie , Tounian Patrick , Clément Karine , Poitou Christine , Dubern Béatrice 
Published: February 2024

Abstract
Background
The determinants of early-onset obesity (< 6 years) are not completely elucidated, however eating behavior has a central role. To date no study has explored eating behavior in children with severe, early-onset obesity. Self-administered questionnaire data from these children were examined to evaluate eating behavior and the etiology of early-onset obesity.

Methods
Children with severe, early-onset obesity (body mass index [BMI] > International Obesity Task Force [IOTF] 30) of different etiologies (hypothalamic obesity [HO], intellectual disability with obesity [IDO], common polygenic obesity [CO]) were prospectively included. BMI history and responses from the Dykens’ Hyperphagia Questionnaire and an in-house Impulsivity Questionnaire at first visit were compared between groups.

Results
This cohort of 75 children (39 girls; mean age ± standard deviation [SD] 10.8 ± 4.4 years) had severe, early-onset obesity at an age of 3.8 ± 2.7 years, with a BMI Z-score of 4.9 ± 1.5. BMI history varied between the 3 groups, with earlier severe obesity in the HO group versus 2 other groups (BMI > IOTF40 at 3.4 ± 1.6 vs. 4.6 ± 1.6 and 8.4 ± 4.1 years for the IDO and CO groups, respectively [P < 0.01]). Absence of adiposity rebound was more prevalent in the HO group (87% vs. 63% and 33% for the IDO and CO groups, respectively [P < 0.01]). The Dykens’ mean total score for the cohort was 22.1 ± 7.2 with no significant between-group differences. Hyperphagia (Dykens’ score > 19) and impulsivity (score > 7) were found in 50 (67%) and 11 children (15%), respectively, with no difference between the HO, IDO and CO groups regarding the number of patients with hyperphagia (10 [67%], 14 [74%], and 26 [63%] children, respectively) or impulsivity (2 [13%], 1 [7%], and 8 [19%] children, respectively). Children with food impulsivity had significantly higher total and severity scores on the Dykens’ Questionnaire versus those without impulsivity.

Conclusion
The Dykens’ and Impulsivity questionnaires can help diagnose severe hyperphagia with/without food impulsivity in children with early-onset obesity, regardless of disease origin. Their systematic use can allow more targeted management of food access control in clinical practice and monitor the evolution of eating behavior in the case of innovative therapeutic targeting hyperphagia.
Synergistic suppression of ovarian cancer by combining NRF2 and GPX4 inhibitors: in vitro and in vivo evidence
Authors: Li Ning , Jiang Xingmei , Zhang Qingyu , Huang Yongmei , Wei Jinbin , Zhang Haitao , Luo Hui 
Published: February 2024

AbstractOvarian cancer is a significant challenge in women's health due to the lack of effective screening and diagnostic methods, often leading to late detection and the highest mortality rate among all gynecologic tumors worldwide. Recent research has shown that ovarian cancer has an "iron addiction" phenotype which makes it vulnerable to ferroptosis inducers. We tested the combination of NRF2-targeted inhibitors with GPX4-targeted inhibitors in ovarian cancer through in vitro and in vivo experiment. The data showed that combination treatment effectively suppressed adherent cell growth, inhibited suspended cell spheroid formation, and restrained the ability of spheroid formation in 3D-culture. Mechanistically, the combination induced accumulation of ROS, 4-HNE, as well as activation of caspase-3 which indicates that this combination simultaneously increases cell ferroptosis and apoptosis. Notably, inhibition of GPX4 or NRF2 can suppress ovarian cancer spreading and growth in the peritoneal cavity of mice, while the combination of NRF2 inhibitor ML385 with GPX4 inhibitors showed a significant synergistic effect compared to individual drug treatment in a syngeneic mouse ovarian cancer model. Overall, these findings suggest that combining NRF2 inhibitors with GPX4 inhibitors results in a synergy suppression of ovarian cancer in vitro and in vivo, and maybe a promising therapeutic strategy for the treatment of ovarian cancer.
A novel AA14 LPMO from Talaromyces rugulosus with bifunctional cellulolytic/hemicellulolytic activity boosted cellulose hydrolysis
Authors: Chen Kaixiang , Zhao Xu , Zhang Peiyu , Long Liangkun , Ding Shaojun 
Published: February 2024

Abstract
Background
The recently discovered PcAA14A and B from white-rot basidiomycete Pycnoporus coccineus enriched our understanding of the oxidative degradation of xylan in fungi, however, the unusual mode of action of AA14 LPMOs has sparked controversy. The substrate specificity and functionality of AA14 LPMOs still remain enigmatic and need further investigation.

Results
In this study, a novel AA14 LPMO was characterized from the ascomycete Talaromyces rugulosus. TrAA14A has a broad substrate specificity with strong oxidative activity on pure amorphous cellulose and xyloglucan. It could simultaneously oxidize cellulose, xylan and xyloglucan in natural hemi/cellulosic substrate such as fibrillated eucalyptus pulp, and released native and oxidized cello-oligosaccharides, xylo-oligosaccharides and xyloglucan oligosaccharides from this substrate, but its cellulolytic/hemicellulolytic activity became weaker as the contents of xylan increase in the alkaline-extracted hemi/cellulosic substrates. The dual cellulolytic/hemicellulolytic activity enables TrAA14A to possess a profound boosting effect on cellulose hydrolysis by cellulolytic enzymes. Structure modelling of TrAA14A revealed that it exhibits a relatively flat active-site surface similar to the active-site surfaces in AA9 LPMOs but quite distinct from PcAA14B, despite TrAA14A is strongly clustered together with AA14 LPMOs. Remarkable difference in electrostatic potentials of L2 and L3 surfaces was also observed among TrAA14A, PcAA14B and NcLPMO9F. We speculated that the unique feature in substrate-binding surface might contribute to the cellulolytic/hemicellulolytic activity of TrAA14A.

Conclusions
The extensive cellulolytic/hemicellulolytic activity on natural hemi/cellulosic substrate indicated that TrAA14A from ascomycete is distinctively different from previously characterized xylan-active AA9 or AA14 LPMOs. It may play as a bifunctional enzyme to decompose some specific network structures formed between cellulose and hemicellulose in the plant cell walls. Our findings shed new insights into the novel substrate specificities and biological functionalities of AA14 LPMOs, and will contribute to developing novel bifunctional LPMOs as the booster in commercial cellulase cocktails to efficiently break down the hemicellulose-cellulose matrix in lignocellulose.
Impact of multimorbidity on the first ts/bDMARD effectiveness and retention rate after two years of follow-up in patients with rheumatoid arthritis from the BIOBADASER registry
Authors: Calvo-Gutiérrez Jerusalem , López-Medina Clementina , Otero-Varela Lucía , Escudero-Contreras Alejandro , Ortega-Castro Rafaela , Ladehesa-Pineda Lourdes , Campos Cristina , Bernabeu-Gonzalvez Pilar , Pérez-Gómez Ana , García-Dorta Alicia , Ruiz-Montesino Dolores , Pombo-Suarez Manuel , Ros-Vilamajo Inmaculada , Sánchez-Alonso Fernando , Castrejón Isabel 
Published: February 2024

Abstract
Background
Patients with Rheumatoid Arthritis (RA) have a higher prevalence of comorbidities compared to the general population. However, the implications of multimorbidity on therapeutic response and treatment retention remain unexplored. Objectives: (a) To evaluate the impact of multimorbidity on the effectiveness of the first targeted synthetic or biologic disease-modifying antirheumatic drug (ts/bDMARD), in patients with RA after 2-year follow-up; (b) to investigate the influence of multimorbidity on treatment retention rate.

Methods
Patients with RA from the BIOBADASER registry exposed to a first ts/bDMARDs were included. Patients were categorized based on multimorbidity status at baseline, defined as a Charlson Comorbidity index (CCI) score ≥ 3. A linear regression model, adjusted for sex and age, was employed to compare the absolute DAS28 score over time after ts/bDMARD initiation between the two groups. The Log-Rank test and Kaplan-Meier curve were used to compare the retention rates of the first ts/bDMARD between the groups.

Results
A total of 1128 patients initiating ts/bDMARD were included, with 107 (9.3%) exhibiting multimorbidity. The linear regression model showed significantly higher DAS28 (beta coefficient 0.33, 95%CI:0.07–0.58) over a two-year period in patients with multimorbidity, even after adjusting for age and sex. Finally, no differences in the ts/bDMARD retention rate were found between groups (median 6.94–6.96 years in CCI < 3 vs. 5.68–5.62 in CCI ≥ 3; p = 0.610).

Conclusions
Multimorbidity in patients with RA was associated with greater DAS28 scores within the first two years after ts/bDMARD initiation, in comparison with patients without multimorbidity. A slightly shorter retention rate was found in patients with multimorbidity, although the difference was non-significant.
Investigation of sports participation motivation in people with disabilities: a cross-sectional study of individuals with physical and hearing impairments
Authors: Ayyildiz Erdem , Aras Dicle , Yagin Fatma Hilal , Gülü Mehmet , Yapici Hakan , Alwhaibi Reem 
Published: February 2024

AbstractWhile reading the literature, it is seen that there are not enough studies on the motivation of disabled individuals to participate in sports. This study aims to examine the sports participation motivations of hearing impaired and physically disabled athletes. This study was a cross-sectional study. The research group of the study consists of physically and hearing-impaired individuals between the ages of 18–47. The participants of this research group consisted of 253 volunteer disabled individuals, 150 of whom were men and 103 of whom were women. Sports participation motivation scale was used for disabled individuals. The scale consists of 3 dimensions and is a 5-point Likert type. The results of the study showed that hearing-impaired people have a higher high school rate and physically person with disability have a higher bachelor’s degree rate, but the primary education rate did not change between hearing and physically person with disability. Physical activity participation differed between hearing and physically person with disability, and it was observed that hearing-impaired people participated in more physical activities. The level of well-being of the physically disabled was significantly better than the hearing impaired. As conclusion, it is observed that the people with the lowest motivation to participate in sports are primary school graduates and those with high welfare have a high motivation to participate in sports.
“DompeKeys”: a set of novel substructure-based descriptors for efficient chemical space mapping, development and structural interpretation of machine learning models, and indexing of large databases
Authors: Manelfi Candida , Tazzari Valerio , Lunghini Filippo , Cerchia Carmen , Fava Anna , Pedretti Alessandro , Stouten Pieter F. W. , Vistoli Giulio , Beccari Andrea Rosario 
Published: February 2024

AbstractThe conversion of chemical structures into computer-readable descriptors, able to capture key structural aspects, is of pivotal importance in the field of cheminformatics and computer-aided drug design. Molecular fingerprints represent a widely employed class of descriptors; however, their generation process is time-consuming for large databases and is susceptible to bias. Therefore, descriptors able to accurately detect predefined structural fragments and devoid of lengthy generation procedures would be highly desirable. To meet additional needs, such descriptors should also be interpretable by medicinal chemists, and suitable for indexing databases with trillions of compounds. To this end, we developed—as integral part of EXSCALATE, Dompé’s end-to-end drug discovery platform—the DompeKeys (DK), a new substructure-based descriptor set, which encodes the chemical features that characterize compounds of pharmaceutical interest. DK represent an exhaustive collection of curated SMARTS strings, defining chemical features at different levels of complexity, from specific functional groups and structural patterns to simpler pharmacophoric points, corresponding to a network of hierarchically interconnected substructures. Because of their extended and hierarchical structure, DK can be used, with good performance, in different kinds of applications. In particular, we demonstrate how they are very well suited for effective mapping of chemical space, as well as substructure search and virtual screening. Notably, the incorporation of DK yields highly performing machine learning models for the prediction of both compounds’ activity and metabolic reaction occurrence. The protocol to generate the DK is freely available at https://dompekeys.exscalate.eu and is fully integrated with the Molecular Anatomy protocol for the generation and analysis of hierarchically interconnected molecular scaffolds and frameworks, thus providing a comprehensive and flexible tool for drug design applications.
Bacterial inoculants and enzymes based silage cocktails boost the ensiling quality of biomasses from reed, corn and rice straw
Authors: Liu Evan Y. , Wang Shuiping , Wang Shibo , Khan Nazir Ahmad , Zhou Xiaoling , Tang Shaoxun , Zhou Chuanshe , Tan Zhiliang , Liu Yong 
Published: February 2024

AbstractThis study investigated the effects of bacterial inoculants and enzyme-based silage cocktails on the dynamics of fermentation, microbiome, and nutritional value of silages produced from low-quality biomasses of reed, rice, and corn straw. A 90-day ensiling trial was performed using five distinct combinations of six basal bacterial species (Lactobacillus plantarum, Lactobacillus buchneri, Pediococcus pentosaceus, Aspergillus niger, Bacillus subtilis, and Candida utilis) and three basal enzymes (xylanase, β-mannanase, and glucanase). Each type of biomass was ensiled with six different treatments, including the Control treatment without an ensiling agent, the basal silage cocktail treatment (Mesa), and Mesa with a double dose of A. niger (MesaA), B. subtilis (MesaB), C. utilis (MesaC) and glucanase (MesaG). The “Mesa” contained (per kg silage), 1.0 × 106 CFU of L. plantarum, 1.4 × 107 CFU L. buchneri, 3.0 × 105 CFU P. pentosaceus, 8.0 × 108 CFU A. niger, 1.6 × 106 CFU B. subtilis and 1.0 × 109 CFU C. utilis, three enzymes (5.0 × 104 U xylanase, 2.5 × 103 U β-mannanase, and 1.0 × 104 U glucanase), and 20 mL molasses. Addition of the silage cocktails significantly improved the fermentation and nutritional quality of the reed, corn, and rice straw silages. Notably, the silage cocktails increased (P < 0.01) the contents of crude protein (CP), ether extract (EE), gross energy (GE), lactic acid (LA), ratio of LA to total acids and ensiling comprehensive evaluation scores, and decreased (P < 0.01) the contents of neutral detergent fiber (NDF), acid detergent fiber (ADF) and pH of reed, corn, and rice straw silages. Regarding the silage microbiome, silage cocktails decreased the relative abundance of Enterobacter and Rahnella1, and increased the relative abundance of Leuconostoc. A. niger, and B. subtilis had a strong positive correlation with CP, EE, GE and Lactobacillus, and a negative correlation with pH, Rhizobium, and Rahnella1 in reed, corn and rice straw silages. In comparison, C. utilis had a strong positive correlation with EE, and a negative correlation with pH, Rhizobium, Stenotrophomonas, and Rahnella1. Glucanase was positively correlated with LA, EE and GE, and negatively correlated with pH and Rahnella1. Silage quality characteristics and microbiome did not differ (P > 0.05) due to the composition of silage cocktails. Based on the comprehensive membership function analysis, the silage comprehensive evaluation scores were highest for double doses of B. subtilis and glucanase for reed, corn, and rice straw. This study revealed that silage cocktails upgraded straw silage fermentation and nutritional quality, and provided a practical solution for the optimal utilization of low-quality straw biomass.
Graphical Abstract
Systemic advantage has a meaningful relationship with grade outcomes in students’ early STEM courses at six research universities
Authors: Castle Sarah D. , Byrd W. Carson , Koester Benjamin P. , Pearson Meaghan I. , Bonem Emily , Caporale Natalia , Cwik Sonja , Denaro Kameryn , Fiorini Stefano , Li Yangqiuting , Mead Chris , Rypkema Heather , Sweeder Ryan D. , Valdivia Medinaceli Montserrat B. , Whitcomb Kyle M. , Brownell Sara E. , Levesque-Bristol Chantal , Molinaro Marco , Singh Chandralekha , McKay Timothy A. , Matz Rebecca L. 
Published: February 2024

AbstractBackgroundLarge introductory lecture courses are frequently post-secondary students’ first formal interaction with science, technology, engineering, and mathematics (STEM) disciplines. Grade outcomes in these courses are often disparate across student populations, which, in turn, has implications for student retention. This study positions such disparities as a manifestation of systemic inequities along the dimensions of sex, race/ethnicity, income, and first-generation status and investigates the extent to which they are similar across peer institutions.ResultsWe examined grade outcomes in a selected set of early STEM courses across six large, public, research-intensive universities in the United States over ten years. In this sample of more than 200,000 STEM course enrollments, we find that course grade benefits increase significantly with the number of systemic advantages students possess at all six institutions. The observed trends in academic outcomes versus advantage are strikingly similar across universities despite the fact that we did not control for differences in grading practices, contexts, and instructor and student populations. The findings are concerning given that these courses are often students’ first post-secondary STEM experiences.ConclusionsSTEM course grades are typically lower than those in other disciplines; students taking them often pay grade penalties. The systemic advantages some student groups experience are correlated with significant reductions in these grade penalties at all six institutions. The consistency of these findings across institutions and courses supports the claim that inequities in STEM education are a systemic problem, driven by factors that go beyond specific courses or individual institutions. Our work provides a basis for the exploration of contexts where inequities are exacerbated or reduced and can be used to advocate for structural change within STEM education. To cultivate more equitable learning environments, we must reckon with how pervasive structural barriers in STEM courses negatively shape the experiences of marginalized students.
Effect of Mineralocorticoid receptor antagonism (MRA) on aldosterone-interleukin 6 axis in heart failure; second opinion. A case-control study
Authors: ElSawi H. , Zidan S. , Elborolosy A. 
Published: February 2024

Abstract
Background
In cases of heart failure characterized by reduced ejection fraction (HFrEF), heightened levels of aldosterone negatively impact the progression of heart failure. Aldosterone exerts its influence through the activation of mineralocorticoid receptors, leading to the subsequent release of IL-6. Recently, the discovery of the role of mineralocorticoid receptor antagonism (MRA) in managing the progression of heart failure, particularly through its effect on IL-6, prompted its inclusion in the American College of Cardiology guidelines. In the years 2019 and 2021, studies elucidated the proinflammatory role of interleukin 6 in the cytokine storm associated with COVID-19, emphasizing the significance of IL-6 inhibitors in controlling this storm. Further research is required to examine the impact of mineralocorticoid receptor antagonism (MRA) on both aldosterone levels and IL-6 release in patients with HFrEF. Additionally, there is a need to assess the effectiveness of current MRA dosages in controlling heart failure with reduced ejection fraction.

Patients and methods
A retrospective analysis was conducted on 108 patients with HFrEF diagnosed through echocardiography. The study covered the period from December 2021 to December 2022. All participants underwent blood tests for aldosterone and interleukin 6 using the ELISA test. The patients were categorized based on cardiac compensation status and the specific mineralocorticoid receptor antagonist (MRA) drug regimen they were on.

Results
There was a notable rise in aldosterone levels and a reduction in serum IL6 observed in 30 patients with Acute Decompensated Heart Failure (ADHF) who were treated with Mineralocorticoid Receptor Antagonists (MRA), as compared to 30 patients with a similar diagnosis who did not receive MRA. Among 24 patients with compensated heart failure using MRA, there was a significant increase in aldosterone levels and a decrease in IL6, in contrast to 24 patients with compensated heart failure who were not on MRA therapy.

Conclusions
In heart failure with reduced ejection fraction (HFrEF), inhibiting mineralocorticoid receptors leads to a reduction in pro-inflammatory IL-6. The action of Mineralocorticoid Receptor Antagonists (MRA) is deemed safe, well-tolerated, and cost-effective when compared to IL-6 inhibitors. There is a need to reevaluate the current MRA regimen with the objective of enhancing its efficacy for optimal reduction in IL-6 and effective control of heart failure progression.
Treatment of a Pial Arterial Venous Fistula in a Newborn: 2-Dimensional Operative Video
Authors: Treffy Randall W. , Hussain Omar , Arocho-Quinones Elsa V. , Hedayat Hirad S. 
Published: February 2024

Pial arterial venous fistulas (PAVFs) are rare vascular entities that occur with direct high-flow connections between pial arterial feeders and large veins without an intervening nidus.
1-5
These vascular abnormalities can present in the pediatric population with high output heart failure.
1
PAVFs can be treated with endovascular intervention, microvascular ligation, or a combination depending on the clinical scenario.
4
Here, we present a case in which a newborn presented in high output heart failure because of a large left-sided middle cerebral artery fed PAVF. We performed a craniotomy for ligation of the PAVF to obliterate the arteriovenous shunting to improve her cardiac status and diminish her intracranial venous hypertension. Throughout the ligation, we used indocyanine green to localize the next appropriate vessels to ligate, allowing us to safely obliterate the anomalous vasculature and improve the patient's cardiac function. Postoperatively, the patient did well neurologically with improvements in cardiac function and near normalization of intracranial vasculature.
The patient's guardians consented to the procedure and to the publication of her image.