bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘I have it, so I understand it, I feel it’: The secondary school experiences of adolescent females with ADHD in England
Authors: Mansfield Eleanor M. G. , Soni Anita 
Published: March 2024

AbstractThis research explores how adolescent females who have been diagnosed with attention deficit hyperactivity disorder (ADHD) experience secondary education in England and make sense of their identity. Within schools, responsibility for supporting this population is placed in the hands of teachers, though prior research suggests that teachers feel underconfident in their ability to do so. Informed by a notion from the disability rights movement ‘nothing about us, without us’ (Charlton, Nothing about us without us: disability oppression and empowerment. Berkeley, CA: University of California Press, 2000), this study places the voice of people with ADHD at the centre of research. Using an interpretivist approach, qualitative data was gathered through unstructured interviews with five participants and was analysed using interpretative phenomenological analysis (IPA). Findings suggested that participants' experiences of education and identity formation were shaped by internal cognitive differences in skills relating to executive function (EF) and sensory differences. The implications of social construction of the ADHD label had an impact, both on how participants understood their identities, and how teaching staff were reported to respond to ADHD‐traits which participants felt they had little control over. Participants reported differences in their perceived ability to self‐advocate and described experiences of attempting to adapt their ADHD‐traits to reduce the risk of social or educational sanction in response to their differences.
An aquaporin and an aquaglyceroporin have roles in low temperature adaptation of mosquitoes (Anopheles sinensis)
Authors: Zhao Yong‐Qiao , Tang Yi‐Ying , Hu Ju‐Ping , Huang Yu‐Zheng , Wan Kai , Zhang Mei‐Hua , Li Ju‐Lin , Zhu Guo‐Ding , Tang Jian‐Xia 
Published: March 2024

AbstractMosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures. Aquaporin channels are found in all life forms, where they facilitate environmental adaptation by allowing rapid trans‐cellular movement of water (classical aquaporins) or water and solutes such as glycerol (aquaglyceroporins). Here, we identified and characterized 2 aquaporin (AQP) homologs in An. sinensis: AsAQP2 (An. sinensis aquaglyceroporin) and AsAQP4 (An. sinensis aquaporin). When expressed in frog (Xenopus laevis) oocytes, AsAQP2 transported water, glycerol, and urea; AsAQP4 transported only water. Water permeation through AsAQP2 and AsAQP4 was inhibited by mercuric chloride. AsAQP2 expression was slightly higher in adult female mosquitoes than in males, and AsAQP4 expression was significantly higher in adult males. The 2 AsAQPs were highly expressed in Malpighian tubules and midgut. AsAQP2 and AsAQP4 expression was up‐regulated by blood feeding compared with sugar feeding. At freezing point (0 °C), the AsAQP4 expression level increased and An. sinensis survival time reduced compared with those at normal temperature (26 °C). At low temperature (8 °C), the AsAQP2 and AsAQP4 expression levels decreased and survival time was significantly longer compared with those at 26 °C. These results suggest that AsAQP2 and AsAQP4 have roles in water homeostasis during blood digestion and in low temperature adaptation of A. sinensis. Together, our results show that the 2 AQPs are important for mosquito diuresis after blood feeding and when exposed to low temperatures.
Immunological parameters of maternal peripheral blood as predictors of future pregnancy outcomes in patients with unexplained recurrent pregnancy loss
Authors: Li Yingrong , Wu Irene X. Y. , Wang Xuan , Song Jinlu , Chen Quan , Zhang Weiru 
Published: March 2024

AbstractIntroductionUnexplained recurrent pregnancy loss (URPL), affecting approximately 1%–5% of women, exhibits a strong association with various maternal factors, particularly immune disorders. However, accurately predicting pregnancy outcomes based on the complex interactions and synergistic effects of various immune parameters without an automated algorithm remains challenging.Material and methodsIn this historical cohort study, we analyzed the medical records of URPL patients treated at Xiangya Hospital, Changsha, China, between January 2020 and October 2022. The primary outcomes included clinical pregnancy and miscarriage. Predictors included complement, autoantibodies, peripheral lymphocytes, immunoglobulins, thromboelastography findings, and serum lipids. Least absolute shrinkage and selection operator (LASSO) analysis and logistic regression analysis was performed for model development. The model's performance, discriminatory, and clinical applicability were assessed using area under the curve (AUC), calibration curve, and decision curve analysis, respectively. Additionally, models were visualized by constructing dynamic and static nomograms.ResultsIn total, 502 patients with URPL were enrolled, of whom 291 (58%) achieved clinical pregnancy and 211 (42%) experienced miscarriage. Notable differences in complement, peripheral lymphocytes, and serum lipids were observed between the two outcome groups. Moreover, URPL patients with elevated peripheral NK cells (absolute counts and proportion), decreased complement levels, and dyslipidemia demonstrated a significantly increased risk of miscarriage. Four models were developed in this study, of which Model 2 demonstrated superior performance with only seven predictors, achieving an AUC of 0.96 (95% CI: 0.93–0.99) and an accuracy of 0.92. A web‐based platform was established to visually present model 2 and to facilitate its utilization by clinicians in outpatient settings (available from: https://yingrongli.shinyapps.io/liyingrong/).ConclusionsOur findings suggest that the implementation of such prediction models could serve as valuable tools for providing comprehensive information and facilitating clinicians in their decision‐making processes.
Angiogenic imbalance in pregnancies with preterm prelabor rupture of membranes between 34 and 37 weeks of gestation
Authors: Kacerovsky Marian , Hornychova Helena , Jaiman Sunil , Pavlikova Ladislava , Holeckova Magdalena , Jacobsson Bo , Tsiartas Panagiotis , Musilova Ivana 
Published: March 2024

AbstractIntroductionThis study aimed to identify whether microbial invasion of the amniotic cavity and/or intra‐amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms‐like tyrosine kinase‐1 (sFlt‐1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations.Material and methodsThis historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra‐amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra‐amniotic inflammation (by amniotic fluid interleukin‐6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt‐1 and PlGF were assessed using the Elecsys® sFlt‐1 and Elecsys® PlGF immunoassays and converted into multiples of medians.ResultsWomen with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt‐1 and sFlt‐1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt‐1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt‐1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt‐1 and sFlt‐1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion.ConclusionsAmong women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra‐amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.
A critical activist orientation predicts lower latent ableist bias
Authors: Gravelle C. Donnan , Sawyer Jeremy E. , Rualo Gavin , Brooks Patricia J. 
Published: March 2024

AbstractDespite legal efforts to reduce societal barriers, people with disabilities still face ableist bias, stereotyping, and stigma. According to the social movement hypothesis, people's participation in and identification with activist movements may reduce bias towards social outgroups. Alternatively, people's intergroup attitudes and bias may influence their participation in activist activities. This study used structural equation modeling to investigate whether reduced bias towards people with disabilities is associated with critical activism and/or personal, familial, or work experience with disability. Undergraduates (N = 497) completed an online survey including measures of ableist bias, critical activist orientation, experience with disability, and demographic characteristics. The relation between having a critical activist orientation and lower ableist bias was bidirectional, suggesting reciprocal influences between individual‐level attitudes and participation in progressive social movements. Aligning with intergroup contact theory, personal (lived) and familial experience with disability correlated with reduced ableist bias, and familial and work experience with having a critical activist orientation. Male gender correlated with increased ableist bias, and male gender, White race, and higher social class with lower endorsements of a critical activist orientation. The results suggest that disability experience and social status influence critical activist identity, which predicts lower bias.
WTAP‐induced N6‐methyladenosine of PD‐L1 blocked T‐cell‐mediated antitumor activity under hypoxia in colorectal cancer
Authors: Liu Qi‐zhi , Zhang Nan , Chen Jun‐yi , Zhou Min‐jun , Zhou De‐hua , Chen Zhuo , Huang Zhen‐xing , Xie Yu‐xiang , Qiao Guang‐lei , Tu Xiao‐huang 
Published: March 2024

AbstractN6‐Methyladenosine (m6A) is a important process regulating gene expression post‐transcriptionally. Programmed death ligand 1 (PD‐L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1‐associated protein (WTAP) degradation caused by ubiquitin‐mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD‐L1 expression in a way that was m6A‐dependent. m6A “reader,” Insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) identified methylated PD‐L1 transcripts and subsequently fixed its mRNA. Additionally, we found that T‐cell proliferation and its cancer cell‐killing effects were prevented by overexpression of WTAP in vitro and in vivo. Overexpression prevented T cells from proliferating and killing CRC by maintaining the expression of PD‐L1. Further evidence supporting the WTAP–PD‐L1 regulatory axis was found in human CRC and organoid tissues. Tumors with high WTAP levels appeared more responsive to anti‐PD1 immunotherapy, when analyzing samples from patients undergoing treatment. Overall, our findings demonstrated a novel PD‐L1 regulatory mechanism by WTAP‐induced mRNA epigenetic regulation and the possible application of targeting WTAP as immunotherapy for tumor hypoxia.
Complete dentures associated with frailty among edentulous older Japanese people: A prospective analysis
Authors: Castrejón‐Pérez Roberto C. , Borges‐Yáñez S. Aída , Ramírez‐Aldana Ricardo , Nasu Ikuo , Saito Yasuhiko 
Published: March 2024

AbstractObjectiveThis study aimed to explore the cross‐sectional and prospective associations between self‐reported functionality of complete dentures (FCD), satisfaction with complete dentures (SCD) and the ability to chew hard food (ACHF) on the one hand and the frailty index (FI) on the other hand among edentulous community‐dwelling older Japanese people.MethodsThe study examined 770 edentulous participants of the Nihon University Japanese Longitudinal Study of Aging. The self‐reported FCD, SCD and ability to chew six groups of food (from hardest to softest) with complete dentures were the independent variables at the baseline. The FI was computed including 40 deficits as the dependent variable at the baseline and 4 years later. Cross‐sectional and prospective generalized linear regression models were fitted controlling for age, gender, marital status, education, working status and area of residence.ResultsThe use of non‐functional complete dentures and dissatisfaction with complete dentures were both associated with a higher FI cross‐sectionally (3.9% [95% CI 2.2–5.6] and 3.2% [95% CI 1.5–4.9], respectively) and prospectively (3.9% [95% CI 2.0–6.0] and 3.3% [95% CI 1.3–5.3], respectively). Regarding the ability to chew, a higher FI at baseline was observed among those able to chew food of Group 2 (1.9%, [95% CI 0.1–3.7]) and Groups 4–6 (1.9%, [95% CI 0.1–3.7]), and a progressive increment in the FI, as the participants reported being able to chew softer groups of food at the follow‐up (Group 2: 2.2% [95% CI 0.05–4.3]; Group 3: 3.6% [95% CI 1.2–6.0]; and Groups 4–6: 3.4 [95% CI 0.7–6.1]).ConclusionSelf‐reported use of non‐functional complete dentures, dissatisfaction with dentures and a reduced ACHF with complete dentures were associated with a higher FI both cross‐sectionally and prospectively.
Dendritic cell‐targeted delivery of antigens using extracellular vesicles for anti‐cancer immunotherapy
Authors: Dang Xuan T. T. , Phung Cao Dai , Lim Claudine Ming Hui , Jayasinghe Migara Kavishka , Ang Jorgen , Tran Thai , Schwarz Herbert , Le Minh T. N. 
Published: March 2024

AbstractNeoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large‐scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell‐derived EVs (RBCEVs) targeting splenic DEC‐205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen‐reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti‐DEC‐205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings.
Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi‐ascending dose study with a bioequivalence arm in healthy volunteers
Authors: Kirkpatrick D. Lynn , Evans Cari , Pestano Linda A. , Millard Jeffrey , Johnston Matthew , Mick Emily , Schmidt William K. 
Published: March 2024

AbstractPF614, a trypsin‐activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two‐part design including a multi‐ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200 mg, n = 6/cohort) or OxyContin (20, 40, or 80 mg; n = 2/cohort) in ascending cohorts, delivered every 12 h for a total of nine doses. In part B, 60 subjects randomized in a four‐way crossover to evaluate BE, received PF614 100 mg and OxyContin 40 mg in fasted and fed (high‐fat diet) states. All subjects were naltrexone blocked prior to first study drug administration to protect against opioid‐related adverse effects; repeat doses were provided on days 1–5. In part A, PF614 was well‐tolerated following twice daily doses of up to 200 mg for 5 days. Plasma oxycodone maximal plasma concentration and area under the concentration time curve increased linearly with increasing doses. Part B showed that plasma oxycodone BE was achieved following 100 mg PF614 or 40 mg OxyContin under both fasted and fed conditions. Additionally, PF614 provided similar oxycodone exposures following both fasted and fed states. This study confirms findings from our single‐ascending dose study, showing that PF614 100 mg releases oxycodone with a PK profile comparable to 40 mg OxyContin under both fasted and fed conditions and with a similar safety profile under naltrexone‐blocked conditions.
The impact of skin color and tone on histamine iontophoresis and Doppler flowmetry measurements as a pharmacodynamic biomarker
Authors: Ramprasad Aarya , Ezekwe Adara , Lee Brian R. , Balasubramanian Shiva , Jones Bridgette L. 
Published: March 2024

AbstractThe phenotypical manifestations of asthma among children are diverse and exhibit varying responses to therapeutic interventions. There is a need to develop objective biomarkers to improve the characterization of allergic and inflammatory responses relevant to asthma to predict therapeutic treatment responses. We have previously investigated histamine iontophoresis with laser Doppler flowmetry (HILD) as a potential surrogate biomarker that characterizes histamine response and may be utilized to guide the treatment of allergic and inflammatory disease. We have identified intra‐individual variability of HILD response type among children and adults with asthma and that HILD response type varied in association with racial classification. As laser Doppler flowimetry may be impacted by skin color, we aimed to further validate the HILD method by determining if skin color or tone is associated with observed HILD response type differences. We conducted an observational study utilizing quantification of skin color and tone obtained from photographs of the skin among participants during HILD assessments via the RGB color model. We compared RGB values across racial, ethnic, and HILD response type via the Kruskal‐Wallis test and calculated Kendall rank correlation coefficient to evaluate the relationship between RGB composite scores and HILD pharmacodynamic measures. We observed that RGB scores differed among racial groups and histamine response phenotypes (p < 0.05). However, there was a lack of correlation between the RGB composite score and HILD pharmacodynamic measures (r values 0.1, p > 0.05). These findings suggest that skin color may not impact HILD response variations, necessitating further research to understand previously observed differences across identified racial groups.
Rate and characteristics of inflammatory neuropathies associated with brentuximab vedotin therapy
Authors: Matthys Arthur , Bardel Benjamin , Le Bras Fabien , Créange Alain , Nordine Tarik , Gounot Romain , Ingen‐Housz‐Oro Saskia , Carvalho Muriel , Lefaucheur Jean‐Pascal , Haioun Corinne , Planté‐Bordeneuve Violaine , Gendre Thierry 
Published: March 2024

AbstractBackground and purposePeripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV‐induced neuropathy (BV‐CN) is a mild distal sensory axonal polyneuropathy. Severe BV‐induced inflammatory neuropathies (BV‐IN) have been described. BV‐IN contribute to lymphoma‐associated morbidity but might be immunotherapy‐responsive. Our primary objective was to evaluate the rate of BV‐IN. Our secondary objectives were to determine risk factors and warning signs.MethodsWe conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV‐induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV‐IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV‐CN.ResultsAmong 83 patients, 41 (49%) developed neuropathy: 35 BV‐CN and 6 BV‐IN. Thus, the rate of BV‐IN was 7.2%. Compared to patients with BV‐CN, no predisposing factor was identified. However, patients with BV‐IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV‐IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy.ConclusionsBrentuximab vedotin‐induced neuropathy is an overlooked complication. Based on four easily identifiable “red flags”, we provide an algorithm to help non‐neurologist physicians that care for BV‐treated patients to detect BV‐IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.
Epidermal growth factor receptor inhibition leads to cellular phenotype correction of DSP‐mutated keratinocytes
Authors: Andrei Daniela , Bremer Jeroen , Kramer Duco , Nijenhuis Albertine M. , van der Molen Marije , Diercks Gilles F. H. , van den Akker Peter C. , Vermeer Mathilde C. S. C. , van der Meer Peter , Bolling Maria C. 
Published: March 2024

AbstractDesmoplakin (DSP) is a desmosomal component expressed in skin and heart, essential for desmosome stability and intermediate filament connection. Pathogenic variants in the DSP gene encoding DSP, lead to heterogeneous skin, adnexa and heart‐related phenotypes, including skin fragility, woolly hair (WH), palmoplantar keratoderma (PPK) and arrhythmogenic/dilated cardiomyopathy (ACM/DCM). The ambiguity of computer‐based prediction analysis of pathogenicity and effect of DSP variants, indicates a necessity for functional analysis. Here, we report a heterozygous DSP variant that was not previously described, NM_004415.4:c.3337C>T (NM_004415.4(NP_004406.2):p.(Arg1113*)) in a patient with PPK, WH and ACM. RNA and protein analysis revealed ~50% reduction of DSP mRNA and protein expression. Patient's keratinocytes showed fragile cell–cell connections and perinuclear retracted intermediate filaments. Epidermal growth factor receptor (EGFR) is a transmembrane protein expressed in the basal epidermal layer involved in proliferation and differentiation, processes that are disrupted in the development of PPK, and in the regulation of the desmosome. In skin of the abovementioned patient, evident EGFR upregulation was observed. EGFR inhibition in patient's keratinocytes strongly increased DSP expression at the plasma membrane, improved intermediate filament connection with the membrane edges and reduced the cell–cell fragility. This cell phenotypic recovery was due to a translocation of DSP to the plasma membrane together with an increased number of desmosomes. These results indicate a therapeutic potential of EGFR inhibitors for disorders caused by DSP haploinsufficiency.