bluuebunny/crossref_metadata_2025_split huggingface dataset:
A p21‐GFP zebrafish model of senescence for rapid testing of senolytics in vivo
Authors: Morsli Samir , Henriques Catarina M. , Ellis Pamela S. , Mortiboys Heather , Baxendale Sarah , Loynes Catherine A. , Renshaw Stephen A. , Bellantuono Ilaria 
Published: April 2023

AbstractSenescence drives the onset and severity of multiple ageing‐associated diseases and frailty. As a result, there has been an increased interest in mechanistic studies and in the search for compounds targeting senescent cells, known as senolytics. Mammalian models are commonly used to test senolytics and generate functional and toxicity data at the level of organs and systems, yet this is expensive and time consuming. Zebrafish share high homology in genes associated with human ageing and disease. They can be genetically modified relatively easily. In larvae, most organs develop within 5 days of fertilisation and are transparent, which allows tracking of fluorescent cells in vivo in real time, testing drug off‐target toxicity and assessment of cellular and phenotypic changes. Here, we have generated a transgenic zebrafish line that expresses green fluorescent protein (GFP) under the promoter of a key senescence marker, p21. We show an increase in p21:GFP+cells in larvae following exposure to ionising radiation and with natural ageing. p21:GFP+cells display other markers of senescence, including senescence‐associated β‐galactosidase and IL6. The observed increase in senescent cells following irradiation is associated with a reduction in the thickness of muscle fibres and mobility, two important ageing phenotypes. We also show that quercetin and dasatinib, two senolytics currently in clinical trials, reduce the number of p21:GFP+cells, in a rapid 5‐day assay. This model provides an important tool to study senescence in a living organism, allowing the rapid selection of senolytics before moving to more expensive and time‐consuming mammalian systems.
Lakota basketball and racism: Performance, performativity, and engaged acrimony
Authors: Klein Alan 
Published: April 2023

SummarySporting contests between communities actively engaged in societal struggle comprise an event I call “engaged acrimony.” In these sporting contests, ideas of sport as promoting harmony get tested and often give way to demonstrations of vitriol that mirror actual relations. In this article, I discuss Lakota basketball teams from Pine Ridge Indian Reservation as they played against neighboring white teams, examining how their responses to racism were safely expressed within and around sporting events. I analyze two of the best‐known instances of engaged acrimony using Turner's sense of performance and Butler's theory of performativity. In doing so, I offer an understanding of how Native communities can fashion an empowering response to racism.
Stability for 6 months and accuracy of a specific enteral caffeine base preparation for a multisite clinical trial
Authors: Erickson Grant , McAnulty Michael , Powers Chelsea , Luong Thu‐Lan , Dobson Nicole R. , Hunt Carl E. 
Published: April 2023

The ‘Intermittent Hypoxia and Caffeine in Infants Born Preterm (ICAF)’ study (NCT03321734) uses an extemporaneously compounded enteral caffeine base solution for its study drug. The primary aim of this report is to determine the stability of this specific enteral caffeine base preparation stored for up to 6 months and assess optimal storage temperature. To analyse stability, caffeine solutions were prepared and stored at 4°C and 25°C (room temperature). The caffeine concentrations were analysed over time using high‐performance liquid chromatography (HPLC). To confirm the accuracy of compounded caffeine concentrations, study drug samples from three research pharmacies were analysed. Stability results showed that caffeine concentrations are within 5% of the expected concentration when stored for up to 6 months at room temperature. Our results also show that accurate caffeine concentrations were achieved by multiple research pharmacies.
Management of luspatercept therapy in patients with transfusion‐dependent β‐thalassaemia
Authors: Sheth Sujit , Taher Ali T. , Coates Thomas D. , Kattamis Antonis , Cappellini Maria Domenica 
Published: April 2023

SummaryPatients with transfusion‐dependent β‐thalassaemia require lifelong, regular red blood cell transfusions for survival; however, frequent blood transfusions are associated with an increased risk of iron overload, transfusion‐transmitted disease and alloimmunization, as well as reduced quality of life. Luspatercept, an erythroid maturation agent that promotes late‐stage erythroid maturation independently of erythropoietin, has demonstrated efficacy in reducing transfusion burden in patients with transfusion‐dependent β‐thalassaemia. In this review, we discuss treatment initiation, ongoing evaluation, dose adjustment and management of adverse events in transfusion‐dependent patients with β‐thalassaemia receiving luspatercept, and we provide guidance on how to determine whether patients are deriving clinical benefit.
Ara h 2‐specific IgE epitope‐like peptides inhibit the binding of IgE to Ara h 2 and suppress lgE‐dependent effector cell activation
Authors: Korošec Peter , Koren Ana , Debeljak Jerneja , Zahirović Abida , Skerbinjek‐Kavalar Maja , Berce Vojko , Dejanović Luka , Luzar Jernej , Štrukelj Borut , Lunder Mojca 
Published: April 2023

AbstractBackgroundClinical and experimental analyses indicate a pathognomonic role for allergen IgE crosslinking through epitope–paratope interactions as a major initial step in the cascade leading to effector cell activation and clinical manifestations of lgE‐mediated food allergies. We aimed to undertake the initial development and assessment of Ara h 2‐specific IgE epitope‐like peptides that can bind to allergen‐specific IgE paratopes and suppress effector cell activation.MethodsWe performed biopanning, screening, IgE binding, selection and mapping of peptides. We generated synthetic peptides for use in all functional experiments. ImmunoCAP inhibition, basophil and mast cell activation tests, with LAD2 cells, a human mast cell line were performed. Twenty‐six children or young adults who had peanut allergy were studied.ResultsWe identified and selected three linear peptides (DHPRFNRDNDVA, DHPRYGP and DHPRFST), and immunoblot analyses revealed binding to lgE from peanut‐allergic individuals. The peptide sequences were aligned to the disordered region corresponding to the loop between helices 2 and 3 of Ara h 2, and conformational mapping showed that the peptides match the surface of Ara h 2 and h 6 but not other peanut allergens. In ImmunoCAP inhibition experiments, the peptides significantly inhibit the binding of IgE to Ara h 2 (p < .001). In basophil and mast cell activation tests, the peptides significantly suppressed Ara h 2‐induced effector cell activation (p < .05) and increased the half‐maximal Ara h 2 effective concentration (p < .05). Binding of the peptides to specific IgEs did not induce activation of basophils or mast cells.ConclusionsThese studies show that the indicated peptides reduce the allergenic activity of Ara h 2 and suppress lgE‐dependent basophil and mast cell activation. These observations may suggest a novel therapeutic strategy for food allergy based on epitope–paratop blocking.
Impact of donor ventricular function on heart transplantation outcomes
Authors: Firoz Ahad , Yanagida Roh , Hamad Eman , Kashem Mohammed , Toyoda Yoshiya 
Published: April 2023

AbstractBackgroundSome heart transplant (HTx) centers have expanded their donor eligibility criteria in response to the organ shortage; one area of active interest involves utilizing hearts with ventricular dysfunction. Our study seeks to identify if a relationship exists between donor left ventricular ejection fraction (LVEF) and ischemic time or donor age on HTx outcomes.MethodsWe performed a retrospective analysis on adult patients who had a HTx between 1996 and 2021 (n = 46,936). Donor LVEF (dLVEF) values were categorized into three groups: <50%, 50%–70%, and >70%. Ischemic time and donor age were stratified into four groups: ≤2.0, 2.1–3.0, 3.1–4.0, >4.0 h, and ≤30, 31–40, 41–50, >50 years, respectively. The outcome of interest was long‐term survival.ResultsMultivariable survival analysis found a slight increase in overall mortality risk for patients with donor ejection fractions <50% (HR = 1.16, p = .013). However, subsequent subgroup investigation discovered that this elevated hazard was only applicable when ischemic time was prolonged to >3.0 h (3.1–4.0 h: HR = 1.23, p = .024; > 4.0 h: HR = 1.52, p < .001). There was no significant difference in survival between dLVEF groups when ischemic time was limited to ≤3.0 h or when stratified by donor age.ConclusionHTx patients with a low donor ejection fraction have comparable survival to recipients with a normal dLVEF when ischemic time is limited to ≤3.0 h. Reduced dLVEF does not appear to be sensitive to advanced donor age. The clinical implications of our study may encourage the recruitment of more donor hearts for transplantation.
Validation of the French version of the Global Functioning: Social and Global Functioning: Role Scales in adolescents and young adults seeking help in early intervention clinics
Authors: Lucarini Valeria , Kazes Mathilde , Krebs Emma , Morin Valentine , Godignon Maud , De Gasquet Marie , Ton Trang , Féron Marion , Tanguy Guillaume , Lévi Agnès , Bellot Cécile , Willard Dominique , Auther Andrea M. , Cornblatt Barbara , Bralet Marie‐Cécile , Krebs Marie‐Odile 
Published: April 2023

AbstractAimSocial and role functioning impairments characterize patients along the schizophrenia spectrum, but the existing evaluations tools do not specifically address younger population issues. The Global Functioning Social (GF:S) and Global Functioning Role (GF:R) scales have been specifically designed for that purpose. The aim of this study is to establish the reliability and concurrent validity of the French version of GF:S and GF:R scales.MethodsThe two scales GF: Social (GF:S) and Role (GF:R) have first been translated into French and independently back translated and validated by the original authors. Between March 2021 and March 2022, we enrolled 51 participants (20.3 ± 3.7 years old; female = 22/51) amongst help‐seekers referring to two different early mental health services in the Île‐de‐France. In an ecological design, participants met different diagnoses, 7 (13.7%) met the criteria for Ultra‐High Risk of psychosis (UHR) using CAARMS criteria.ResultsInter‐rater reliability was excellent for scores related to the past month and to the higher levels of functioning over the past year. Both scales showed good to excellent concurrent validity as measured by correlation with the Social and Occupational Functioning Assessment Scale (SOFAS) and the Personal and Social Performance Scale (PSP).ConclusionOverall, this study confirms the reliability and validity of the French version of the GF:S and GF:R scales. The use of these scales may improve the evaluation of social and occupational functioning in French‐speaking young help‐seekers, in a transdiagnostic approach, both in clinical and research settings.
Sequencing and combination of currentsmall‐moleculeinhibitors for chronic lymphocytic leukemia: Where is the evidence?
Authors: Chung Clement , Umoru Godsfavour , Abboud Karen , Hobaugh Eleanor 
Published: April 2023

AbstractSmall‐molecule inhibitors have revolutionized the treatment of chronic lymphocytic leukemia (CLL), a landscape once dominated by chemoimmunotherapy (i.e., an anti‐CD20 monoclonal antibody in combination with systemic chemotherapy) in fit and unfit individuals. Key challenges include the management of refractory disease as well as the optimization of the therapy sequence. Decreased responsiveness has been observed with prolonged treatment, especially with Bruton tyrosine kinase (BTK) and phosphatidylinositol 3‐kinase (PI3K) inhibitors which are given continuously, while venetoclax, an agent that targets dysregulations in intrinsic apoptosis signaling, has a fixed duration when combined with anti‐CD20 monoclonal antibodies or BTK inhibitors. Combination therapy aims to synergistically target different oncogenic signaling pathways to abrogate the proliferation of resistant clones and thereby allows for fixed‐duration treatments. An advantage of fixed‐duration therapy is the potential to decrease financial and drug‐induced toxicities. Sequencing of therapies is important to individualize treatment decisions based on factors such as age, comorbidities, tolerability, and patient preferences. However, to date, there are limited data to guide the rational sequencing or combination of these therapies, since conventional chemoimmunotherapy or chemotherapy regimens were used as comparators against these small‐molecule inhibitors in trials that led to their regulatory approvals. In this article, we examined and evaluated the current evidence for sequencing versus the combination of small‐molecule inhibitors for CLL by conducting comprehensive searches of the United States National Library of Medicine PubMed database, key meeting abstracts, and clinical practice guidelines. We also summarized findings from expert opinions to elucidate best practices for clinical scenarios with limited evidence to guide treatment selection.
A mammal and bird's‐eye‐view of the pupil during sleep and wakefulness
Authors: Ungurean Gianina , Rattenborg Niels C. 
Published: April 2023

AbstractBesides regulating the amount of light that reaches the retina, fluctuations in pupil size also occur in isoluminant conditions during accommodation, during movement and in relation to cognitive workload, attention and emotion. Recent studies in mammals and birds revealed that the pupils are also highly dynamic in the dark during sleep. However, despite exhibiting similar sleep states (rapid eye movement [REM] and non‐REM [NREM] sleep), wake and sleep state‐dependent changes in pupil size are opposite between mammals and birds, due in part to differences in the type (striated vs. smooth) and control of the iris muscles. Given the link between pupil dynamics and cognitive processes occurring during wakefulness, sleep‐related changes in pupil size might indicate when related processes are occurring during sleep. Moreover, the divergent pupillary behaviour observed between mammals and birds raises the possibility that changes in pupil size in birds are a readout of processes not reflected in the mammalian pupil.
Patterns of response to anti‐calcitonin gene‐related peptide monoclonal antibodies during first 6 months of treatment in resistant migraine patients: Impact on outcome
Authors: Torres‐Ferrus Marta , Gallardo Victor J. , Alpuente Alicia , Caronna Edoardo , Giné‐Ciprés Eulalia , Pozo‐Rosich Patricia 
Published: April 2023

AbstractBackground and purposeThe response pattern to monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP MAbs) shown in migraine prevention clinical trials is not always reproducible at an individual level. This study was undertaken to describe patterns of start and consistency of the response to anti‐CGRP MAbs during the first 6 months of treatment and the association with baseline clinical characteristics.MethodsThis is a prospective clinical cohort observational study. We included migraine patients treated with erenumab or galcanezumab evaluated at baseline and after 3 and 6 months (M3, M6) of treatment. The response was categorized according to reduction in monthly headache days (MHD): Sustained‐response (SustainedR, ≥50% at M3 and M6), Short‐Response (ShortR, M3 ≥50% and M6 <50%), Late‐Response (LateR, M3 <50% and M6 ≥50%), Limited‐Response (LimitedR, 25%–50% at M3 and M6), and No‐Response (NoR, <25% at M3 and M6). Response patterns were compared at baseline and with outcome variables at M3 and M6.ResultsWe included 357 patients with a headache frequency of 21.0 (interquartile range = 16.0–28.0) MHD, and 84.0% (300/357) were chronic migraine. The distribution according to response pattern was 37.0% (110/297) SustainedR, 16.8% (50/297) LateR, 10.4% (31/297) ShortR, 22.6% (67/297) LimitedR, and 13.1% NoR (39/297). The SustainedR and LateR groups showed statistically significant anxiety and depression score reduction at M3 and M6 compared to the other groups.ConclusionsInitial response to anti‐CGRP MAbs is not consistent in all patients. Persistence of anxiety and depression might be associated with lower response rates at M6.
Teaching English to young learners in private sector of Iranian ELT: Challenges and local realities
Authors: Tavakol Mahbube , Tavakoli Mansoor 
Published: April 2023

AbstractThe growing phenomenon of (pre)primary English education worldwide has resulted in the rise in prominence of the discipline of teaching English to young learners (TEYL). Under the global forces and parents' pressure, early EFL learning has also turned into a pervasive trend in the marketized private sector of Iranian ELT as evidenced by the ever‐growing number of classes of ever‐younger learners. However, it is not clear what stands at its core because it has not received the attention it deserves, and reports on its status quo are almost non‐existent. This qualitative study was conducted to shine the spotlight on some local realities and challenges faced by Iranian TEYL to trigger more intensive research and informed discussion into this Cinderella area of scholarship. The findings regarding each aspect are presented and discussed along with implications and directions for future research.
Multilevel calibration procedure for the oral health national multicenter survey in primary teeth
Authors: Markovic Dejan , Vukovic Ana , Soldatovic Ivan , Peric Tamara , Kilibarda Biljana , Rosianu Ruxandra Sava , Campus Guglielmo 
Published: April 2023

AbstractBackgroundEarly childhood caries (ECC) requires systematically collected and standardized data.AimTo describe a novel multilevel calibration procedure in primary dentition.DesignCalibration method involved two calibration levels: the first (L1) involved an interexaminer agreement between three main investigators, the group leaders (GLs) in the following level; the second level (L2) involved three groups of 11 paediatric dentists and interexaminer agreement assessment according to the GLs in each group. The study sample consisted of 650 primary teeth surfaces in eight children (mean age 6.56 ± 2.22 years). Surface‐by‐surface percent agreement, tooth‐by‐tooth percent agreement, Cohen's kappa, and Fleiss kappa statistics were used to calculate interexaminer reliability. Statistical analysis was performed with SPSS 27.0.ResultsSurface‐by‐surface percent agreement regarding ICDASepi‐merged revealed almost perfect agreement (>90.00%) on both L1 and L2. Kappa values and ranges showed good agreement at both L1 (overall κ = .95) and L2 (overall κ = .98) and almost perfect consistency was detected between GLs at L1 (>91.30%) and substantial agreement at L2 (>85.00%). All examiners at L2 showed almost perfect positive agreement (sensitivity = 96.77%–100%) when detecting the presence of dental plaque.ConclusionThe calibration procedure appeared feasible prior to organizing multicenter epidemiological oral health survey in large population groups of preschool children, with higher number of examiners.
A nonlinear autoregressive distributed lag analysis on the macroeconomic effect of global oil price in the Philippines
Authors: Deluna Roperto S. , Tatlonghari Virgilio M. , Loanzon Jeanette Isabelle V. 
Published: April 2023

AbstractStudies have pointed out that oil price volatility influenced economic output and growth among developing and net oil‐importing countries. More than a quarter of the Philippines’ energy demand depends on crude oil, and 99% of the crude oil demand is imported mainly from the Middle East. This study was conducted to determine if there is a nonlinear or asymmetric output response to oil price movements and examine which economic sector in the Philippines is the most vulnerable to oil shocks. This contributes to the literature for a case of developing, oil importing, inflation targeting and post‐oil industry deregulated economy. A nonlinear autoregressive distributive lag model was applied to observe quarterly data from 1998:Q1 to 2019:Q4 of the relevant economic variables. Results revealed an asymmetric effect of non‐oil variables on sectoral performance. World oil prices affect economic sector outputs symmetrically or linearly. The service sector is found to be the most vulnerable sector to oil price shocks. The absence of asymmetry can be attributed to increased competition in the Philippines’ domestic oil industry brought about by oil market deregulation. Improving the energy mix and reducing oil intensity is vital to offset any oil price shock transmission to an oil‐importing economy like the Philippines.
Food assessment for pesticide's contamination in Chugchilán parish crops in Cotopaxi (Ecuador)
Authors: Oviedo‐Chávez Augusto César , Rojas‐González Edgar Wilson , Vinueza‐Galárraga Julio César , Andrade‐Zurita Myriam Jicela , Sarmiento‐Sarmiento Nelly Guadalupe , Ochsner‐Mera Rosmerie 
Published: April 2023

AbstractThe objective of this study is to evaluate the contamination by pesticides in food grown in the parish of Chugchilán. From 258 families that were part of the main project, a sub‐sample of 26 families was obtained and, for each of them, a sample of food was extracted and evaluated by chromatographic methods. The main pesticides found in the locality are from the group of organophosphates, carbamates, dithiocarbamates, and glyphosate. Contamination by organophosphates, carbamates, and dithiocarbamates is well below the maximum residue limits while glyphosate is found in most foods exceeding the maximum residue limit, mainly in radish with 8.36 mg/kg being the limit of .1 mg/kg. There is evidence of contamination in food by pesticides, however, the values obtained are below the maximum residue limits with the exception of glyphosate. Organochlorines usage was not detected in any sample.Practical applicationsThis study may be of interest to the scientific community as it learns about the impact of pesticides on population food security, mainly vulnerable. Similarly, it can be a contribution to the agricultural community interested in eliminating pesticides from their production by implementing new cultivation techniques that are friendly to the environment and consumers health. It benefits the population of Chugchilán, since the information about the crops in the area allowing them to take actions and strategies that improve food quality and its population health.