bluuebunny/crossref_metadata_2025_split huggingface dataset:
New quinazolinone‐based derivatives as DHFR/EGFR‐TK inhibitors: Synthesis, molecular modeling simulations, and anticancer activity
Authors: El‐Gazzar Yomna I. , Ghaiad Heba R. , El Kerdawy Ahmed M. , George Riham F. , Georgey Hanan H. , Youssef Khairia M. , El‐Subbagh Hussein I. 
Published: October 2022

AbstractNew 2‐mercapto‐quinazolin‐4‐one analogs were synthesized and tested for their in vitro anticancer activity, dihydrofolate reductase (DHFR) inhibition, and epidermal growth factor tyrosine kinase (EGFR‐TK) inhibition activities. Compound24, which is characterized by a 2‐benzyl‐thio function, showed broad‐spectrum anticancer activity with high safety profile and selectivity index. The concentrations of24causing 50% growth inhibition (GI50) and total cell growth inhibition (TGI) and its lethal concentration 50 (LC50) were 15.1, 52.5, and 91.2 µM, respectively, using 5‐fluorouracil as a positive control. Also, it showed EGFR‐TK inhibitory activity with IC50 = 13.40 nM compared to gefitinib (IC50 = 18.14 nM) and DHFR inhibitory potency with 0.30 μM compared to methotrexate (MTX; IC50 = 0.08 μM). In addition, compound24caused cell cycle arrest and apoptosis on COLO‐205 colon cancer cells. Compounds37, 21, and54showed remarkable DHFR inhibitory activity with IC50values of 0.03, 0.08, and 0.08 μM, respectively. The inhibitory properties of these compounds are due to an electron‐withdrawing group on the quinazolinone ring, except for compound54. In a molecular modeling study, compound24showed the same binding mode as gefitinib as it interacted with the amino acid Lys745 via π–π interaction. Compound37showed a similar binding mode as MTX through the binding interaction with Lys68, Asn64 via hydrogen bond acceptor, and Phe31 via arene–arene interaction. The obtained model and substitution pattern could be used for further development.
Association of Antibodies to Prevotella copri in Anti–Cyclic Citrullinated Peptide‐Positive Individuals At Risk of Developing Rheumatoid Arthritis and in Patients With Early or Established Rheumatoid Arthritis
Authors: Seifert Jennifer A. , Bemis Elizabeth A. , Ramsden Kristina , Lowell Cassidy , Polinski Kristen , Feser Marie , Fleischer Chelsie , Demoruelle M. Kristen , Buckner Jane , Gregersen Peter K. , Keating Richard M. , Mikuls Ted R. , O'Dell James R. , Weisman Michael H. , Deane Kevin D. , Norris Jill M. , Steere Allen C. , Holers V. Michael 
Published: October 2022

ObjectivePrevotella copri (P copri), a gut commensal, has been reported to be an immune‐relevant organism in individuals with rheumatoid arthritis (RA). This study sought to evaluate anti–P copri (anti–Pc) antibody responses in our participant cohorts and to determine when in the natural history of RA such responses develop.MethodsWe analyzed serum levels of immunoglobulin A (IgA) and IgG antibodies from a 27‐kd protein of P copri (anti–Pc‐p27), an immunogenic P copri protein, in study participants at risk of developing RA, participants who transitioned to RA, participants with early RA (<1 year of disease), and participants with established RA, with comparisons made to their matched controls. We also evaluated anti–Pc‐p27 antibody levels in individuals stratified by RA‐related autoantibody status.ResultsOverall, participants with RA had significantly higher IgA anti–Pc‐p27 antibody levels and trended toward higher IgG anti–Pc‐p27 antibody levels compared with matched controls. When stratified by early versus established RA, participants with early RA had median IgG anti–Pc‐p27 antibody levels that were overall higher, whereas median IgA anti–Pc‐p27 antibody levels were statistically significantly higher in participants with established RA compared with their matched controls. In the autoantibody‐specific analyses, the at‐risk population with anti–cyclic citrullinated peptide (anti‐CCP) antibodies, but not rheumatoid factor (RF), trended toward increased levels of IgG anti–Pc‐p27. Additionally, RA participants who were seropositive for both CCP and RF had significantly increased levels of IgA anti–Pc‐p27 antibodies and trended toward higher levels of IgG anti–Pc‐p27 antibodies compared with matched controls.ConclusionOur findings support a potential etiologic role for P copri in both RA preclinical evolution and the subsequent pathogenesis of synovitis.
Can drawing instruction help students with low visuospatial ability in learning anatomy?
Authors: Ritchie Helen E. , Oakes Diana , Drury Helen , Ollerenshaw Suzanne , Hegedus Elizabeth 
Published: October 2022

AbstractVisuospatial skills are considered important attributes when learning anatomy and there is evidence suggesting that this ability can be improved with training techniques including drawing. The Mental Rotations Test (MRT) has been routinely used to assess visuospatial ability. This study aimed to introduce students to drawing as a learning strategy for anatomy. Undergraduate speech science anatomy students took part in a drawing tutorial (n = 92), completed an MRT test, pre‐ and post‐tutorial tests, and surveys regarding their use and attitudes toward drawing as a study tool. The impact on their examination performance was then assessed. Regardless of MRT score or attitude to drawing, students who participated in the drawing tutorial demonstrated immediate improvement in post‐tutorial test scores. Students in the drawing group performed better in most anatomy components of the examination, but the result did not reach statistical significance. There was only a positive correlation between MRT score and one type of anatomy question (non‐image‐based) and speech physics questions (r = 0.315,p = 0.002). The unexpected finding may relate to the MRT which assesses spatial rather than object visualization skills. Students who liked drawing also performed significantly better in word‐based and speech physics questions. It is likely that the style of identification question did not require the mental manipulation ability assessed in the MRT. This study demonstrated that students with lower MRT scores are not outperformed in all aspects of anatomy assessment. The study highlights the importance of a more nuanced understanding of visuospatial skills required in anatomy.
System identification and improved internal model control for yaw of unmanned helicopter
Authors: Huang Linjie , Pei Hailong , Cheng Zihuan 
Published: October 2022

AbstractThe sea breeze is a low‐frequency disturbance that severely damages the stability of small unmanned helicopters operating over the sea, especially for the yaw control, which is highly sensitive to disturbance. General internal model control is an appropriate method for dealing with this kind of operation conditions, whereas conventional internal model control cannot eliminate the tracking errors between a nominal model and a real model. In coping with unknown dynamics and low‐frequency gust disturbances for small helicopters, this paper proposes a novel robust controller constructed with system identification and integrator‐based improved general internal model. As a refinement of the conventional frame, the proposed control scheme extends the applicable scope of a controlled plant from a priori known dynamic to an unknown dynamic. Furthermore, under the proposed controller, it is guaranteed that the tracking error between the actual model and the nominal model converges to zero asymptotically. Finally, the effectiveness and advantage of the proposed control scheme are verified through comparative practical flight tests.
Using percentiles in the interpretation of Patient‐Reported Outcomes Measurement Information System scores: Guidelines for autism
Authors: Schuchard Julia , Kaplan‐Kahn Elizabeth A. , Carle Adam C. , Holmes Laura Graham , Law Kiely , Miller Judith S. , Parish‐Morris Julia , Forrest Christopher B. 
Published: October 2022

AbstractThe objectives of this study were to (1) demonstrate the application of percentiles to advance the interpretation of patient‐reported outcomes and (2) establish autism‐specific percentiles for four Patient‐Reported Outcomes Measurement Information System (PROMIS) measures. PROMIS measures were completed by parents of autistic children and adolescents ages 5–17 years as part of two studies (n = 939 parents in the first study and n = 406 parents in the second study). Data from the first study were used to develop autism‐specific percentiles for PROMIS parent‐proxy sleep disturbance, sleep‐related impairment, fatigue, and anxiety. Previously established United States general population percentiles were applied to interpret PROMIS scores in both studies. Results of logistic regression models showed that parent‐reported material hardship was associated with scoring in the moderate–severe range (defined as ≥75th percentile in the general population) on all four PROMIS measures (odds ratios 1.7–2.2). In the second study, the percentage of children with severe scores (defined as ≥95th percentile in the general population) was 30% for anxiety, 25% for sleep disturbance, and 17% for sleep‐related impairment, indicating a high burden of these problems among autistic children. Few children had scores at or above the autism‐specific 95th percentile on these measures (3%–4%), indicating that their scores were similar to other autistic children. The general population and condition‐specific percentiles provide two complementary reference points to aid interpretation of PROMIS scores, including corresponding severity categories that are comparable across different PROMIS measures.
Cognitive function in late‐stage HFpEF patients with tricuspid regurgitation undergoing transcatheter tricuspid valve intervention
Authors: Gerçek Muhammed , Irimie Anca A. , Gerçek Mustafa , Fox Henrik , Fortmeier Vera , Rudolph Tanja K. , Rudolph Volker , Friedrichs Kai P. 
Published: October 2022

AbstractObjectivesThis study evaluates the impact of transcatheter tricuspid valve interventions (TTVI) on cognitive function (CF), quality of life (QOL), and exercise capacity in late‐stage heart failure with preserved ejection fraction (HFpEF) and relevant tricuspid regurgitation (TR).BackgroundReduced cardiac output (CO) critically affects CF. Severe TR aggravates CO reduction in HFpEF, while TTVI has been demonstrated to re‐establish CO to a significant extent. The effect of TTVI on CF of HFpEF patients has so far not been investigated.MethodsAssessment of CF was performed using the standardized Montreal Cognitive Assessment test in 34 symptomatic HFpEF patients with at least severe TR before and 3 months after TTVI alongside echocardiographic examinations and assessment of exercise capacity and QOL.ResultsMedian age of the patients was 81.0 [78.8; 83.0] years and 50.0% were female. CF was impaired in 67.6% of the patients. TR ≤ moderate was achieved in 94.1% of the cases. Overall CF improved significantly (from 20.6 ± 3.9 to 23.0 ± 4.4; p = 0.001). Particularly, significant improvements were identified in the executive function (p < 0.001) and memory (p = 0.008). In addition, linear regression analysis demonstrated a significant collinearity of improvement between executive function as well as memory and increased CO (ρ = 0.695; p < 0.001 and ρ = 0.628; p < 0.001, respectively). The walked distance and QOL also improved significantly 3 months after TTVI.ConclusionCognitive impairment is highly prevalent in HFpEF patients with severe TR. TTVI results in an improved CF, especially with regard to executive function and memory. These improvements also correlate with more efficient hemodynamics reflected by increased CO.
Stability of Pt10Sn3 Clusters Supported on γ‐Al2O3 in Oxidizing Environment: a DFT Comparison of Alloying and Size Effects
Authors: Shahrokhi Masoud , Chizallet Celine , Loffreda David , Raybaud Pascal 
Published: October 2022

AbstractThe understanding of the structure and properties of γ‐Al2O3 supported platinum‐tin catalysts in oxidizing conditions is of prominent importance for many catalytic reactions. By using density functional theory calculations and ab initio molecular dynamics simulations, we identify the adsorption sites of oxygen atoms on a Pt10Sn3/γ‐Al2O3(100) cluster model and analyze its reconstruction and electronic charge redistribution. A strengthening of O adsorption is found for the cluster with respect to the Pt3Sn(111) surface, due to the key role of Al−Pt interfacial sites at low coverage, the ductility and the metastability of the cluster. Moreover, the ab initio (
, T) thermodynamic phase diagrams show only minor differences between the supported Pt10Sn3 and Pt13 clusters. Both clusters are much more oxidized than their homologous Pt and Pt3Sn(111) surfaces, and their oxygen contents may exceed 1 ML. This suggests a stronger size effect than an alloying effect for the oxidation of the metallic PtSn nanoparticles at small size.
Discovery of Anti‐tubercular Analogues of Bedaquiline with Modified A‐, B‐ and C‐Ring Subunits
Authors: Barbaro Lisa , Nagalingam Gayathri , Triccas James A. , Tan Lendl , West Nicholas P. , Priebbenow Daniel L. , Baell Jonathan B. 
Published: October 2022

AbstractTo date, the clinical use of the anti‐tubercular therapy bedaquiline has been somewhat limited due to safety concerns. Recent investigations determined that modification of the B‐ and C‐ring units of bedaquiline delivered new diarylquinolines (for example TBAJ‐587) with potent anti‐tubercular activity yet an improved safety profile due to reduced affinity for the hERG channel. Building on our recent discovery that substitution of the quinoline motif (the A‐ring subunit) for C5‐aryl pyridine groups within bedaquiline analogues led to retention of anti‐tubercular activity, we investigated the concurrent modification of A‐, B‐ and C‐ring units within bedaquiline variants. This led to the discovery that 4‐trifluoromethoxyphenyl and 4‐chlorophenyl pyridyl analogues of TBAJ‐587 retained relatively potent anti‐tubercular activity and for the 4‐chlorophenyl derivative in particular, a significant reduction in hERG inhibition relative to bedaquiline was achieved, demonstrating that modifications of the A‐, B‐ and C‐ring units within the bedaquiline structure is a viable strategy for the design of effective, yet safer (and less lipophilic) anti‐tubercular compounds.
Intraoral clinical examinations of pediatric patients with anticipatory anxiety and situational fear facilitated by therapy dog assistance: A pilot RCT
Authors: Gussgard Anne M. , Carlstedt Kerstin , Meirik Malin 
Published: October 2022

AbstractObjectiveTo evaluate whether the presence of a certified therapy dog specially trained for working in a dental setting may facilitate dental care of anxious pediatric patients.MethodsThe Norwegian Regional Committee for Medical and Health Research Ethics approved a randomized cross‐over trial with a study sample of n = 16 children aged between 6 and 12 years. The trial was registered on clinicaltrials.gov. Pediatric patients referred to specialist care at the Public Dental Service Competence Center of Northern Norway (TkNN) because of anxiety were invited to partake in the trial. Study participants met twice for an intraoral examination by a specialist pediatric dentist. Per random allocation, a therapy dog team was present in the clinic operatory during the clinical examination on the first or the second visit. The primary outcome was the assessment of patient compliance during the intraoral examination (yes/no). Secondary outcomes were measurements of child satisfaction and anxiety using the CFSS‐DS scale (Dental subscale of Children's Fear Survey Schedule) completed by a parent/guardian. Supplementary outcomes were salivary cortisol level, heart rate variability, and skin conductance.ResultsTen boys and six girls (mean age 8.5) were recruited. All completed both clinical visits and demonstrated full compliance while undergoing a dental examination. All study participants and guardians reported great satisfaction. The salivary cortisol level reduction during the clinical examination on the first visit decreased by 30% in the presence of the therapy dog and 20% without, while the decrease during the clinical examination on the second visit was 29% in the presence of the therapy dog and 3% without. Within the limitations of the experimental setup, the electrophysiological measurements were unreliable in the current study population.ConclusionDog‐assisted therapy in a dental care setting appears to have a positive effect on children with dental anxiety or children that avoid dental care.
Landau damping of ion‐acoustic waves with simultaneous effects of non‐extensivity and non‐thermality in the presence of hybrid Cairns‐Tsallis distributed electrons
Authors: Bilal Muhammad , Rehman Aman‐ur‐ , Mahmood Shahzad , Shahzad Muhammad Ahsan , Sarfraz Muhammad 
Published: October 2022

AbstractThe dispersion properties and Landau damping rate of ion‐acoustic waves (IAWs) with the hybrid Cairns‐Tsallis distributed (CTD) electrons and Maxwellian ions are investigated using the plasma kinetic model based on Vlasov‐Poisson's equations. For both super‐extensive (q < 1) and sub‐extensive (q > 1) plasmas, the dielectric response function, real frequency, and Landau damping rate of IAWs are derived. By taking the effect of θi, e (ion‐to‐electron temperature ratio) into account, it is found that with the increase of ion temperature, the real frequency and wave dispersion effects increase as well (for both super‐extensive and sub‐extensive cases). Exploring the properties of the Landau damping rate of IAWs with the simultaneous presence of non‐thermal parameter α and non‐extensive parameter q, a comparison of numerical and analytical results is presented. It is found that in different ranges of θe, i (electron‐to‐ion temperature ratio), on decreasing the values of the non‐extensive parameter and increasing values of the non‐thermal parameter, the weak damping rate is observed (vice versa) in super‐extensive or super‐thermal plasma, although the trend of the damping rate in sub‐thermal plasma is similar (as in the case of super‐thermal plasma) but is less weak. It is further revealed that the damping rate of IAWs in thermal plasmas (Maxwellian) is stronger than the damping rate of IAWs in the case of non‐thermal plasmas (CTD). The current study is applicable to provide deep insight and further allow the exploration of electrostatic plasma modes in different space and laboratory plasma environments where the hybrid CTD plasma exists.
Initial assemblage characteristics determine the functional dynamics of flower‐strip plant communities
Authors: Gardarin Antoine , Valantin‐Morison Muriel 
Published: October 2022

AbstractIn agroecosystems, species‐rich habitats, such as linear field margins and flower strips, are beneficial to the overall biodiversity and contribute to pest control. Their effects are thought to be mediated by plant species composition and diversity. However, the management of plant communities with targeted levels of functional diversity has been little investigated. In an open field landscape, we compared the effects of the sown species richness (9, 14, and 29 species) and functional diversity (high vs. low) of eight different seed mixtures, sown in flower strips, on the 4‐year temporal dynamics of their functional diversity. There was a good agreement between the expected and realized species richness and functional diversity at the start of the experiment. All plant assemblages progressively lost species over time, but this decline was lower for assemblages sown with a high initial functional diversity, in which species evenness was maintained at higher levels. Species‐rich assemblages had a higher degree of functional redundancy, and their functional diversity remained higher over time than less rich assemblages. A possible explanation for this is that functional redundancy would have enabled the compensation for the loss of species by functionally equivalent species. The realized functional diversity of the sown species also limited the establishment of spontaneous species, perhaps due to a higher degree of niche occupancy. This study provides useful insight into the creation of functionally diversified plant communities. A high level of initial species and functional diversity is required to guarantee a greater temporal persistence of the communities.
Environmental DNA (eDNA) detects temporal and habitat effects on community composition and endangered species in ephemeral ecosystems: A case study in vernal pools
Authors: Ruiz‐Ramos Dannise V. , Meyer Rachel S. , Toews Daniel , Stephens Molly , Kolster Monique K. , Sexton Jason P. 
Published: October 2022

AbstractVernal pools are temporary wetlands that can form during a rainy season, often in Mediterranean climates, and serve as ideal testing grounds to understand species detection using eDNA and how biological communities may shift across time and spatial and environmental heterogeneity. Most vernal pools exhibit high plant and animal diversity and endemism, but due to their ephemeral nature, they are understudied, especially their microorganisms. Habitat destruction and fragmentation creates an urgent need to monitor their biodiversity, but traditional species surveys require time and taxonomic expertise. We conducted a community science‐enabled examination of soil environmental DNA (eDNA) in California's Great Central Valley and assessed the capacity of eDNA to aid biomonitoring. We used metabarcoding of16S,ITS1,CO1,18S, andITS2marker regions to quantify and compare differences in pool communities across two sampling periods (during years with disparate precipitation) and to estimate variation among pools and inundation zones (vernal pool bottom, transitional edge, and grassland upland). We found differences in beta diversity among sampling periods, pools, and inundation zones; alpha diversity was mainly affected by sampling period and zone, but this differed by marker. Numerous taxonomic families varied in abundance and composition among samples, yet vernal pool communities remained distinct from upland grass communities, even between sampling periods differing by 1 year. Turnover in ecologically co‐occurring taxon pairs varied by over 90% between sampling periods in all metabarcodes but plants, which were more stable. Finally, we confirmed substantial concordance between eDNA and traditional inventories of the reserve's plants and presented a case in which we detected one endangered plant species, Colusa grass (Neostapfia colusana), in advance of its emergence. This initial study adds hundreds of new taxon records for California vernal pools and discusses benefits and challenges of using eDNA for biomonitoring within stressful, temporary, or otherwise challenging ecosystems.