bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic potential of hesperidin in diabetes mellitus‐induced erectile dysfunction through Nrf2‐mediated ferroptosis and oxidative stress
Authors: Xin Sheng , Song Wen , Mao Jiaquan , Hu Peng , Chen Zhong , Liu Jihong , Song Xiaodong , Fang Qian , Cui Kai 
Published: November 2024

AbstractBackgroundAmong erectile dysfunction (ED) caused by metabolic abnormalities, diabetes mellitus‐induced ED (DMED) progresses rapidly, manifests with severe symptoms, and shows reduced responsiveness to conventional medications. Hyperglycemia in the corpus cavernosum has been linked to the induction of both ferroptosis and oxidative stress, which are mediated by nuclear factor E2 related factor 2 (Nrf2). Hesperidin (Hes), a flavonoid compound, has been revealed to activate Nrf2 in certain diabetic complications, yet the efficacy of Hes on DMED and the specific mechanism remain unclear.ObjectivesTo elucidate the potential mechanism and efficacy of Hes in regulating Nrf2‐mediated ferroptosis and oxidative stress in DMED.Materials and methodsDMED rats were constructed through the intraperitoneal injection of streptozotocin (STZ), partially supplemented with Hes. In parallel, in vitro research utilized human umbilical vein endothelial cells (HUVECs), with glucose addition to simulating a high glucose (HG) environment, and induced with Hes or ML385 (an Nrf2 inhibitor). Penile tissues and HUVECs were harvested for subsequent analyses.ResultsThe results of this study indicate that Hes partially reversed the impaired erectile function. The expression of Nrf2, glutathione peroxidase 4 (GPX4), and heme oxygenase‐1 (HO‐1) in the corpus cavernosum elevated after supplementing with Hes, resulted in an inhibition in ferroptosis and oxidative stress. Moreover, the quantity and function of erectile effector cells were restored, and cavernous fibrosis was ameliorated. In HG‐induced HUVECs, Hes ameliorated Nrf2‐mediated ferroptosis and oxidative stress, effects which ML385 partially reversed.ConclusionsHes exerts a therapeutic effect on DMED rats and a regulatory mechanism on the Nrf2–HO‐1/GPX4 axis, concurrently revitalizing endothelial and smooth muscle cells, and diminishing fibrosis. Our study provides robust preclinical evidence for employing Hes in treating DMED.
How Much Does the Business Development of Circular Eco‐Efficient Practices Improve by Shaking Stakeholders up?
Authors: Garces‐Ayerbe Concepción , Rivera‐Torres Pilar , Darmandieu Aurore 
Published: November 2024

ABSTRACTEuropean firms are currently in a process of transition toward a circular economy, which is expected to guarantee sustainable growth over time. Developing eco‐efficient practices is a necessary step in this transition. This study analyzes the impact of stakeholder engagement in a circular business ecosystem on the development of these circular eco‐efficient practices. Past literature has evidenced the impact of stakeholder environmental pressure on firm strategic decisions and outcomes. We adopt the stakeholder theory from a more recent vision, arguing that “shaking stakeholders up” within a circular ecosystem is a more advanced strategy than the traditional approach of reacting to stakeholder pressure. Using structural equation modeling, we examine the data of 14,726 European firms and their relationships with five primary stakeholder groups. The results offer theoretical and empirical support for the idea that firms can go further in adopting eco‐efficient circular practices by shaking stakeholders up, selecting them, and managing relationships with them.
Novel BRAT1 Deep Intronic Variant Affects Splicing Regulatory Elements Causing Cerebellar Hypoplasia Syndrome: Genotypic and Phenotypic Expansion
Authors: Poleg Tomer , Proskorovski‐Ohayon Regina , Dolgin Vadim , Hadar Noam , Safran Amit , Agam Nadav , Jean Matan M. , Freund Ofek , Gradstein Libe , Shelef Ilan , Sadaka Yair , Birk Ohad S. 
Published: November 2024

ABSTRACTBiallelic mutations in BRAT1 result in lethal neonatal rigidity and multifocal seizure syndrome and a milder neurodevelopmental disorder of cerebellar atrophy with or without seizures (NEDCAS, MIM 618056). Combining linkage analysis and whole‐genome sequencing (WGS), we identified a novel deep intronic BRAT1 variant, NC_000007.14 (NM_152743.4):c.128‐1585 T > G, in 3 siblings of a consanguineous Bedouin family exhibiting NEDCAS. In silico analyses followed by molecular studies demonstrated this variant's impact on splice regulatory elements, forming a cryptic exon, resulting in a deleterious frameshift and aberrant transcript. Previously reported pathogenic BRAT1 splice‐site mutations were adjacent to exons, affecting canonical consensus splice sites, and identifiable by whole‐exome sequencing. The deep intronic BRAT1 disease‐causing variant is thus unique and underscores the potential of intronic splice regulatory elements in BRAT1 disease pathogenesis, demonstrating the utility of WGS in identifying noncoding variants in unresolved cases. The affected individuals (deep into their twenties) are among the longest‐surviving patients described to date—delineating the NEDCAS phenotype at these ages. Although sharing homozygosity of the same variant, they show varying penetrance of nystagmus and extreme variability in the extent of ataxia and age of onset of developmental delay. Notably, we summarize all documented BRAT1 splice variants reported to date and their phenotypic associations.
Prevalence, pattern, contact sensitisers and impact on quality‐of‐life of occupational dermatitis among beekeepers in North India
Authors: Qayoom Misbah , Hassan Iffat , Jeelani Shazia 
Published: November 2024

AbstractBackgroundBeekeepers face specific occupational health risks due to exposure to bee products and chemicals. Propolis is a notable cause of contact hypersensitivity in beekeepers. Its chemical composition varies by region, complicating allergy investigations. While propolis allergies are documented in Western populations, no studies exist in India.AimTo assess the prevalence and patterns of dermatitis among beekeepers, identify contact sensitisers and evaluate its impact on quality‐of‐life (QoL).MethodsAn 18‐month community‐based cross‐sectional study was conducted involving 340 beekeepers from the Kashmir Valley in North India. Data collection included personal interviews, dermatological examinations and patch testing using self‐made antigens of propolis, beeswax, royal jelly and standardised Baseline Indian Standard Series. The Dermatology Life Quality Index (DLQI) was used to measure the impact of dermatitis on QoL.ResultsDermatitis prevalence among beekeepers was 17.1%, with the majority presenting with hand eczema. Onset or worsening of dermatitis was reported by 77.6% after working in apiaries. Significant associations were found with duration of beekeeping (p < 0.05) and a history of atopy (p < 0.001). Patch testing revealed 27.5% of beekeepers with positive reactions, primarily to propolis (10% in pet). The mean DLQI score was 3.5, indicating a generally small impact on QoL.ConclusionDermatitis was a common occupational condition among beekeepers, strongly associated with the duration of beekeeping and a history of atopy, though its overall impact on QoL was limited. Propolis emerged as a primary sensitiser in the study population.
Evaluation of Heterogeneity in the Coding Region of BRAF, MAP2K1, and MAP2K2 Genes in Primary and Metastatic Melanomas
Authors: Fernandes Mariana , Barcelos Denise , Carapeto Fernando Cintra Lopes , Cardili Leonardo , Comodo Andreia Neves , Mazloum Susana Fares , Marins Maryana Mara , Mendes Agatha Ribeiro , Pesquero João Bosco , Landman Gilles 
Published: November 2024

ABSTRACTIntroductionThe incidence of melanoma has been increasing in recent decades. BRAF mutations appear in 50%–70% of melanomas. The BRAF‐targeted therapy increased the disease‐free survival of patients with metastatic melanoma, but this response may be short, due to several resistance mechanisms, such as the presence of other subclones with mutations. Evaluation of mutations and heterogeneity in the coding region of the BRAF, MAP2K1, and MAP2K2 genes in primary and metastatic melanomas.Patients and MethodsTwenty‐seven samples of primary and metastatic superficial spreading melanoma (SSM) and acral lentiginous melanoma (ALM) were analyzed for BRAF, MAP2K1, and MAP2K2 mutations using the next‐generation sequencing technique.ResultsIn ALM, the mutation rate found was 50% in the BRAF and MAP2K1 genes and 28.6% in MAP2K2. In the SSM, BRAF was mutated in 76.9%, MAP2K1 in 30.8%, and MAP2K2 in 23.2% of the cases. All samples were formed by distinct tumor subclones in the same lesion. Intertumoral heterogeneity was present between primary and metastatic lesions of ALM in BRAF, MAP2K1, and MAP2K2; the cases of SSM were heterogeneous for BRAF and MAP2K1.ConclusionWe sought to evaluate the mutations in the BRAF, MAP2K1, and MAP2K2 genes, revealing a heterogeneous mutation profile in samples of ALM and SSM.
Parental perspectives following the implementation of advanced hybrid closed‐loop therapy in children and adolescents with type 1 diabetes and elevated glycaemia
Authors: Lai Sin‐ting Tiffany , Styles Sara E. , Boucsein Alisa , Zhou Yongwen , Michaels Venus , Jefferies Craig , Wilshire Esko , De Bock Martin I. , Wheeler Benjamin J. 
Published: November 2024

AbstractAimsTo identify from a parental perspective facilitators and barriers of effective implementation of advanced hybrid closed‐loop (AHCL) therapy in children and adolescents with type 1 diabetes (T1D) with elevated glycaemia.MethodsSemi‐structured interviews were conducted with parents of participants while in a post‐trial extension phase of the CO‐PILOT randomized controlled trial. The Capability, Opportunity, Motivation, Behaviour Model and Theoretical Domain Framework informed the interviews and framework analysis.ResultsEleven parents of 9 children and adolescents were interviewed. The median age of their children and adolescents was 14.2 years (IQR 13.3–14.7) with median HbA1c 78 mmol/mol (IQR 75–86) (9.3% IQR 9–10) before starting AHCL. Facilitators of implementing AHCL therapy included the following: (1) knowledge acquired from training, (2) establishing routines and action plans, (3) remote glucose monitoring, (4) achievement of glycaemic goals through automation, (5) children/adolescents' capability to use AHCL independently, (6) improved outcomes incentivized continued AHCL, (7) optimism about sustained improvements and (8) social support from healthcare providers, school staff, peers and parents. Barriers to AHCL implementation included the following: (1) challenges with device usability, (2) need for technical support, (3) forgotten knowledge and skills, (4) non‐adherence to best practices, (5) negative social influences, (6) physical and psychosocial burden and (7) negative emotions.ConclusionsThis study provides comprehensive insights into parental perspectives of influences on implementing AHCL therapy in children and adolescents with elevated glycaemia. As parents remain key partners in diabetes care, these findings inform successful implementation of AHCL and development of future diabetes technology.
Natriuretic peptide levels and predicting risk of developing new diabetes mellitus and metabolic syndrome
Authors: Singh Jasraj , Adel Fadi W. , Scott Christopher G. , Chen Horng H. 
Published: November 2024

AbstractAimsDefine the relationship between N‐terminal atrial natriuretic peptide (NT‐ANP) levels and incident metabolic syndrome and type 2 diabetes mellitus (‘metabolic disease’) in healthy adults and develop a risk prediction score.Materials and MethodsRetrospective cohort study of Olmsted County Heart Function Study participants, a random sampling of county residents aged 45 years and older (n = 2042). Clinical data were collected during enrolment between 1997 and 2000 and upon follow‐up 4 years later. Outcomes were followed for 8 years. We studied 715 subjects without metabolic disease at enrolment who completed follow‐up, assessing incident metabolic disease as the primary outcome. Youden's index was used to identify optimal cut‐points and develop the risk score.ResultsUpon multivariate analysis adjusting for age gender, HDL and triglycerides, higher baseline serum NT‐ANP levels were associated with a lower risk of metabolic disease (OR: 0.65, CI 0.49–0.85, p = 0.002). Higher baseline serum insulin and aldosterone levels were associated with higher risk of incident metabolic disease (OR: 2.04, CI 1.57–2.65, p < 0.001; OR: 1.43, CI 1.14–1.81, p = 0.002, respectively). Baseline serum NT‐ANP < 3337 pg/mL was 96.6% sensitive for future development of metabolic disease. A weighted score including all three biomarkers was 78.6% sensitive and 77.3% specific.ConclusionsIn healthy adults aged 45 years or older, higher baseline NT‐ANP levels are associated with a lower four‐year risk of developing metabolic disease. Serum NT‐ANP levels are a sensitive biomarker of future risk of metabolic disease and have screening utility when combined with insulin and aldosterone levels into a composite score.
Multimodality Imaging in Chronic Constrictive Pericarditis
Authors: Karamarkou Christina , Maltsinioti Charalampia , Bruder Oliver , Babady Mehran 
Published: November 2024

ABSTRACTThis case highlights the use of multimodality imaging in the diagnosis and management of chronic constrictive pericarditis (CP) in a 37‐year‐old male with a history of T‐wave inversions on electrocardiogram (ECG). The patient underwent adenosine stress cardiac magnetic resonance (CMR) due to suspicion of coronary artery disease (CAD). CMR revealed findings suggestive of chronic CP, including pericardial thickening and septal shudder, with computed tomography (CT) confirming the presence of pericardial calcification. The diagnosis was established through the combination of CMR and CT imaging. The patient underwent a successful pericardiectomy. This case emphasizes the crucial role of CMR and CT in diagnosing and guiding the management of CP.
Attenuated processing of task‐irrelevant speech and other auditory stimuli: fMRI evidence from arithmetic tasks
Authors: Ylinen Artturi , Hannula‐Sormunen Minna , McMullen Jake , Lehtinen Erno , Wikman Patrik , Alho Kimmo 
Published: November 2024

AbstractWhen performing cognitive tasks in noisy conditions, the brain needs to maintain task performance while additionally controlling the processing of task‐irrelevant and potentially distracting auditory stimuli. Previous research indicates that a fundamental mechanism by which this control is achieved is the attenuation of task‐irrelevant processing, especially in conditions with high task demands. However, it remains unclear whether the processing of complex naturalistic sounds can be modulated as easily as that of simpler ones. To address this issue, the present fMRI study examined whether activity related to task‐irrelevant meaningful speech is attenuated similarly as that related to meaningless control sounds (nonsense speech and noise‐vocoded, unintelligible sounds). The sounds were presented concurrently with three numerical tasks varying in difficulty: an easy control task requiring no calculation, a ‘routine’ arithmetic calculation task and a more demanding ‘creative’ arithmetic task, where solutions are generated to reach a given answer. Consistent with their differing difficulty, the tasks activated fronto‐parieto‐temporal regions parametrically (creative > routine > control). In bilateral auditory regions, activity related to the speech stimuli decreased as task demands increased. Importantly, however, the attenuation was more pronounced for meaningful than nonsense speech, demonstrating that distractor type can strongly modulate the extent of the attenuation. This also suggests that semantic processing may be especially susceptible to attenuation under conditions with increased task demands. Finally, as this is the first study to utilize the ‘creative’ arithmetic task, we conducted exploratory analyses to examine its potential in assessing neural processes involved in mathematical problem‐solving beyond routine arithmetic.
Patterns of Gene Flow in Anopheles coluzzii Populations From Two African Oceanic Islands
Authors: Campos Melina , Rašić Gordana , Viegas João , Cornel Anthony J. , Pinto João , Lanzaro Gregory C. 
Published: November 2024

ABSTRACTThe malaria vector Anopheles coluzzii is widespread across West Africa and is the sole vector species on the islands of São Tomé and Príncipe. Our interest in the population genetics of this species on these islands is part of an assessment of their suitability for a field trial involving the release of genetically engineered A. coluzzii. The engineered construct includes two genes that encode anti‐Plasmodium peptides, along with a Cas9‐based gene drive. We investigated gene flow among A. coluzzii subpopulations on each island to estimate dispersal rates between sites. Sampling covered the known range of A. coluzzii on both islands. Spatial autocorrelation suggests 7 km to be the likely extent of dispersal of this species, whereas estimates based on a convolutional neural network were roughly 3 km. This difference highlights the complexity of dispersal dynamics and the value of using multiple approaches. Our analysis also revealed weak heterogeneity among populations within each island but did identify areas weakly resistant or permissive of gene flow. Overall, A. coluzzii on each of the two islands exist as single Mendelian populations. We expect that a gene construct that includes a low‐threshold gene drive and has minimal fitness impact should, once introduced, spread relatively unimpeded across each island.
Integrating Anthropogenic–Pesticide Interactions Into a Soil Health‐Microbial Index for Sustainable Agriculture at Global Scale
Authors: Xu Nuohan , Chen Bingfeng , Wang Yan , Lei Chaotang , Zhang Zhenyan , Ye Yangqing , Jin Mingkang , Zhang Qi , Lu Tao , Dong Huaping , Shou Jianxin , Penuelas Josep , Zhu Yong‐Guan , Qian Haifeng 
Published: November 2024

ABSTRACTSoil microbiota in intensive agriculture are threatened by pesticides, economic activities, and land‐use changes. However, the interactions among these anthropogenic factors remain underexplored. By analyzing 2356 soil metagenomes from around the world, we developed a comprehensive soil health‐microbial index that integrates microbial diversity, nutrient cycling potential, metabolic potential, primary productivity, and health risks to assess how the soil microbiota respond to anthropogenic factors. Our results indicated that the health‐microbial index was the lowest with severe pesticide contamination. Pesticides, in combination with other anthropogenic and climatic factors, exacerbate the decline in this index. Machine learning predictions suggest that the health‐microbial index in approximately 26% of global farmland could decline between 2015 and 2040, even under sustainable development scenarios. Even with strategies to reduce pesticide usage, we cannot completely halt the decline in the health‐microbial index. Our findings highlight that sustaining soil microbial health on a global scale requires addressing not only pesticide management but also broader anthropogenic impacts.
Image Analysis Characterizes Phenotypic Variation in the Growth of Mushroom‐Forming Fungus Schizophyllum commune
Authors: Matsumae Hiromi , Sudo Megumi , Imanishi Tadashi , Hosoya Tsuyoshi 
Published: November 2024

ABSTRACTSchizophyllum commune, a common wood‐decay mushroom known for its extremely high genetic variation and as a rare cause of human respiratory diseases, could be a promising model fungus contributing to both biology and medicine. To better understand its phenotypic variation, we developed an image analysis system that quantifies morphological and physiological traits of mycelial colonies in Petri dishes. This study evaluated growth of six wild and one clinical isolates of Japanese S. commune, subjected to different temperatures and glucose concentrations, including a condition mimicking the human respiratory environment. Our analysis revealed that combinations of two growth indices, area and whiteness, and profiling by clustering algorithms highlighted strain‐specific responses. For example, the clinical isolate was the whitest under the respiratory‐like condition. We also found that the growth rate was strongly determined by glucose concentration, while the effects of temperature on growth varied among the strains, suggesting that while glucose preference is common in this species, responses to temperature differ between strains. This system showed sufficient sensitivity to detect variation in mycelial growth. Our study provides a key to unraveling morphological and physiological traits behind the high polymorphisms in S. commune, including the ability to colonize the human respiratory tract.
Pedagogical Translanguaging for Epistemic Inclusion: Scaffolding Strategies in Bilingual Subject Instruction in Norway
Authors: Moraczewska Agnieszka 
Published: November 2024

ABSTRACTBilingual subject instruction (BSI) is one form of language support classes in Norwegian schools, preparing students from language minorities for mainstream instruction by combining subject and language tutoring through the students’ home language. This article examines interactions within a Polish–Norwegian classroom setting, focusing on the concept of pedagogical translanguaging and scaffolding for epistemic inclusion of student resources. Grounded in the framework of translanguaging pedagogy and scaffolding techniques for student comprehension and production, the study involves a micro‐analysis of recorded dyadic interactions between a bilingual teacher and three students in individual BSI classes. The findings highlight language shifts as integral to teacher–student interactions, demonstrating the diligent use of scaffolding techniques for co‐constructing knowledge. The study underscores the mediating role of translanguaging practices in supporting both content and language knowledge, emphasizing the active integration of students’ previous knowledge and experiences for fostering epistemic inclusion.
Push and pull factors in return migration intentions among first‐generation Croatian migrants in Germany and Ireland
Authors: Liu Yang Vincent , Kutnjak Ivković Sanja , Pavlović Vinogradac Valentina 
Published: November 2024

AbstractWhy are some migrants more willing to move back to their homeland than others? Using a mixed methods approach, this article sheds light on the factors contributing to the desire for return migration among first‐generation Croatian migrants (N = 499). In particular, the current study focuses on the role that migrants' trust in state institutions in both their homeland and current countries of residence plays in their desire to return to the homeland. Quantitative analyses reveal that factors of institutional trust strongly correlate with migrants' willingness to return to Croatia, as do short‐term visits and (dis)satisfaction with their current lives, particularly for those who left Croatia for personal reasons instead of institutional ones. The qualitative results suggest that the pull factors of return migration tend to be personal, while the push factors are largely institutional. In addition, the idea of a “future” for both the returnees (e.g. financial stability) and the country (e.g. political conditions) is the key to migrants' decision‐making about returning.