bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term safety and efficacy of adjunctive lacosamide in the treatment of generalized onset tonic–clonic seizures: An open‐label extension trial
Authors: Vossler David G. , Farkas Mark Kristof , Poverennova Irina , Watanabe Masako , Conrath Peter , Dimova Svetlana , McClung Carrie , Roebling Robert , Williams Paulette , O'Brien Terence J. ,   the EP0012 Study Group
Published: October 2024

AbstractObjectiveThis study was undertaken to assess long‐term safety, tolerability, and efficacy of lacosamide (LCM) as adjunctive therapy for generalized onset tonic–clonic seizures (GTCS) in patients aged ≥4 years with idiopathic generalized epilepsy (IGE).MethodsEP0012 (NCT02408549) was a phase 3, multicenter, open‐label extension (OLE) trial. Patients were enrolled from SP0982 (NCT02408523). Trial duration was ≥2 years (adults) and ≤5 years (children). The trial consisted of a treatment period, ≤4‐week taper period, and 30‐day safety follow‐up. Safety (primary) variables were incidence of treatment‐emergent adverse events (TEAEs), discontinuations due to TEAEs, incidence of onset of absence or myoclonic seizures, and increase in days with absence or myoclonic seizures per 28 days. Efficacy (secondary) variable was percent change in GTCS frequency per 28 days. Kaplan–Meier estimated retention rates and analyses by number of lifetime antiseizure medications (ASMs) were performed post hoc.ResultsOverall, 239 patients (mean age = 27.9 years, 56.1% female, 18.4% children) were enrolled and received ≥1 dose of LCM in this OLE (median treatment duration = 3.2 years); 157 (65.7%) completed the trial, and 82 (34.3%) discontinued. The most common reason for discontinuation (≥10%) was withdrawn consent (30 [12.6%]). Kaplan–Meier estimated retention rate was 87%, 72%, and 60% at 1, 3, and 5 years, respectively. Overall, 222 (92.9%) patients reported TEAEs; 19 (7.9%) discontinued due to TEAEs. Few patients had an increase in number of days with absence or myoclonic seizures, or incidence of new absence or myoclonic seizures. Median percent change in GTCS frequency per 28 days from the combined baseline was −88.6% (range = −100.0 to 465.4, n = 238). Post hoc analyses demonstrated small numerical differences between patients with 1, 2, and ≥3 lifetime ASMs.SignificanceThe results support the use of long‐term adjunctive LCM for GTCS in patients with IGE. Long‐term adjunctive LCM was efficacious and well tolerated independent of the number of ASMs used before LCM initiation.Clinical trial registration: ClinicalTrials.gov: NCT02408549.
Mouse models of Slc35a2 brain mosaicism reveal mechanisms of mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy
Authors: Yoon Hyojung , Ringland Amanda , Anderson James J. , Sran Sahibjot , Elziny Soad , Huynh Cindy , Shinagawa Noriyuki , Badertscher Samantha , Corrigan Rachel R. , Mashburn‐Warren Lauren , Amari Foued , Chen Min , Coppola Vincenzo , Crino Peter B. , Bedrosian Tracy A. 
Published: October 2024

AbstractObjectiveBrain somatic variants in SLC35A2 were recently identified as a genetic marker for mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). The role of SLC35A2 in cortical development and the contributions of abnormal neurons and oligodendrocytes to seizure activity in MOGHE remain largely unexplored.MethodsHere, we generated a novel Slc35a2 floxed allele, which we used to develop two Slc35a2 conditional knockout mouse lines targeting (1) the Emx1 dorsal telencephalic lineage (excitatory neurons and glia) and (2) the Olig2 lineage (oligodendrocytes). We examined brain structure, behavior, and seizure activity.ResultsKnockout of Slc35a2 from the Emx1 lineage, which targets both cortical neurons and oligodendrocytes, resulted in early lethality and caused abnormal cortical development, increased oligodendroglial cell density, early onset seizures, and developmental delays akin to what is observed in patients with MOGHE. By tracing neuronal development with 5‐Ethynyl‐2'‐deoxyuridine (EdU) birthdating experiments, we found that Slc35a2 deficiency disrupts corticogenesis by delaying radial migration of neurons from the subventricular zone. To discern the contributions of oligodendrocytes to these phenotypes, we knocked out Slc35a2 from the Olig2 lineage. This recapitulated the increased oligodendroglial cell density and resulted in abnormal electroencephalographic activity, but without a clear seizure phenotype, suggesting Slc35a2 deficiency in neurons is required for epileptogenesis.SignificanceThis study presents two novel Slc35a2 conditional knockout mouse models and characterizes the effects on brain development, behavior, and epileptogenesis. Together, these results demonstrate a direct causal role for SLC35A2 in MOGHE‐like phenotypes, including a critical role in neuronal migration during brain development, and identify neurons as key contributors to SLC35A2‐related epileptogenesis.
Leveraging Unsupervised Task Adaptation and Semi‐Supervised Learning With Semantic‐Enriched Representations for Online Sexism Detection
Authors: Rodríguez‐Sánchez Francisco , Carrillo‐de‐Albornoz Jorge , Plaza Laura 
Published: October 2024

ABSTRACTOver the past decade, the proliferation of hateful and sexist content targeting women on social media has become a concerning issue, adversely affecting women's lives and freedom of expression. Previous efforts to detect online sexism have utilized monolingual ensemble transformers combined with data augmentation techniques that incorporate related‐domain data, such as hate speech. However, these approaches often struggle to capture the full diversity and complexity of sexism due to limitations in the size and quality of training data. In this study, we introduce a novel sexism detection system that employs in‐domain unlabeled data through unsupervised task‐adaptation techniques and semi‐supervised learning, using an efficient single multilingual transformer model. Additionally, we incorporate a Sentence‐BERT layer to enhance our system with semantically meaningful sentence embeddings. Our proposed system outperforms existing state‐of‐the‐art methods across all tasks and datasets, demonstrating its effectiveness in detecting and addressing sexism in social media text. These results underscore the potential of our approach, providing a foundation for further research and practical applications.
“You and me”: Parental perceptions on asymmetry in twins' development and their dominance relationship dynamics
Authors: Segal Hila , Rum Yonat , Barkan Adi , Knafo‐Noam Ariel 
Published: October 2024

AbstractObjectiveThis study investigated the role of nontypical development in the relative dominance in twins' relationships throughout childhood.BackgroundDominance dynamics, affecting siblings' well‐being, are different in twins than in singletons for whom age and development often dictate sibling hierarchy. These dynamics in twins, who share similar ages and developmental contexts, remain underexplored and demand further understanding.MethodA longitudinal study surveyed 1,547 mothers and 536 fathers of 322 monozygotic (sharing nearly 100% genes) and 1,199 dizygotic (sharing 50% genetic variance) twin pairs, aged 3 to 8–9. Both parents reported on the twins' relationships. Mothers reported whether either twin had a developmental condition.ResultsNo dominance difference was found in similar developmental conditions dyads, whether both twins had typical or nontypical development. However, in dyads where twins differed in the developmental condition, nontypically developing twins were less dominant than their typically developing cotwins. This dominance imbalance persisted throughout childhood, even if initial developmental issues were resolved.ConclusionFrom parents' perspectives, nontypical development does not, in itself, prevent children from demonstrating dominance behaviors in twinship, but it is more likely that the asymmetry in developmental conditions is associated with the relationship between the twins.Implications and RecommendationsAccording to parents' perceptions, twins with nontypical development might experience imbalances in their relationship throughout childhood when their co‐twin is a typically developing child. However, demonstrating dominance might be possible for them in other contexts. Understanding these dominance dynamics is vital for caregivers, informing tailored parenting strategies and interventions to support the well‐being of children.
Integration of plant and microbial oil processing at oilcane biorefineries for more sustainable biofuel production
Authors: Cortés‐Peña Yoel R. , Woodruff William , Banerjee Shivali , Li Yalin , Singh Vijay , Rao Christopher V. , Guest Jeremy S. 
Published: October 2024

AbstractOilcane—an oil‐accumulating crop engineered from sugarcane—and microbial oil have the potential to improve renewable oil production and help meet the expected demand for bioderived oleochemicals and fuels. To assess the potential synergies of processing both plant and microbial oils, the economic and environmental implications of integrating microbial oil production at oilcane and sugarcane biorefineries were characterized. Due to decreased crop yields that lead to higher simulated feedstock prices and lower biorefinery capacities, current oilcane prototypes result in higher costs and carbon intensities than microbial oil from sugarcane. To inform oilcane feedstock development, we calculated the required biomass yields (as a function of oil content) for oilcane to achieve financial parity with sugarcane. At 10 dw% oil, oilcane can sustain up to 30% less yield than sugarcane and still be more profitable in all simulated scenarios. Assuming continued improvements in microbial oil production from cane juice, achieving this target results in a minimum biodiesel selling price of 1.34 [0.90, 1.85] USD∙L−1 (presented as median [5th, 95th] percentiles), a carbon intensity of 0.51 [0.47, 0.55] kg CO2e L−1, and a total biodiesel yield of 2140 [1870, 2410] L ha−1 year−1. Compared to biofuel production from soybean, this outcome is equivalent to 3.0–3.9 as much biofuel per hectare of land and a 57%–63% reduction in carbon intensity. While only 20% of simulated scenarios fell within the market price range of biodiesel (0.45–1.11 USD∙L−1), if the oilcane biomass yield would improve to 25.6 DMT∙ha−1∙y−1 (an equivalent yield to sugarcane) 87% of evaluated scenarios would have a minimum biodiesel selling price within or below the market price range.
“Das Problem des Stilwandels”: Stylistic Transformation in the Work of Emil Staiger
Authors: Ronzheimer Elisa 
Published: October 2024

AbstractThis article reconstructs a theoretical and methodological problem in the work of German literary scholar Emil Staiger, a representative of the postwar school of Werkimmanenz, which called for a renewal of form‐sensitive practices of reading. It analyzes Staiger's notion of style and traces its application in his monumental Goethe monograph and his essay collection Stilwandel, highlighting the difficulties that arise from Staiger's attempt to operationalize style in the sense of an artwork's inner unity (“Einstimmigkeit”) for his study of dynamic and changing forms. These difficulties led him to reframe his notion of style in a 1968 paper that, however, ultimately left the problem of how to write a history of literary styles unresolved.
Factors associated with low hepatitis B surface antigen levels in chronic hepatitis B patients treated with nucleot(s)ide analogs
Authors: Suzuki Takanori , Matsuura Kentaro , Inoue Takako , Kawamura Hayato , Fujiwara Kei , Kataoka Hiromi , Tanaka Yasuhito 
Published: October 2024

AbstractObjectivesSeveral studies have reported that chronic hepatitis B (CHB) patients with low hepatitis B surface antigen (HBsAg) levels (100 or 10 IU/mL) at the cessation of nucleot(s)ide analogs (NA) have a favorable prognosis. In this retrospective study, we evaluated the duration of NA treatment and the factors associated with achieving these low HBsAg levels. We also examined the relationship between HBsAg and hepatitis B core‐related antigen (HBcrAg) levels at the time of NA discontinuation and subsequent clinical outcomes.MethodsThis study included 153 CHB patients who initiated NA therapy at our hospital, received treatment, and were followed up for over 1 year.ResultsThe cumulative incidence rates of achieving low HBsAg levels at 5 and 10 years post‐NA administration were as follows: 19.0% and 29.2% for HBsAg <100 IU/mL, 13.8% and 17.6% for HBsAg <10 IU/mL, and 9.5% and 13.5% for HBsAg <0.05 IU/mL, respectively. Hepatitis B virus genotypes other than genotype C (hazard ratio [HR] 3.47; p < 0.001) and an HBsAg level <1000 IU/mL at the start of NA therapy (HR 2.49; p = 0.008) were significantly associated with achieving HBsAg levels <100 IU/mL. Among 27 patients who discontinued NA therapy, 5 patients with HBsAg levels <100 IU/mL and HBcrAg levels <3 log U/mL at the time of discontinuation did not experience virological relapse.ConclusionsThe cumulative rates of achieving HBsAg levels <100 IU/mL were relatively high. Discontinuation of NA may be considered based on HBsAg and HBcrAg levels during the course of NA therapy.
Mechanical loading‐induced alveolar bone remodeling is suppressed in the diabetic state via the impairment of the specificity protein 1/vascular endothelial growth factor (SP1/VEGF) axis
Authors: Hoshino Rina , Nakamura Nobuhisa , Yamauchi Taisuke , Aoki Yuki , Miyabe Megumi , Sasajima Sachiko , Ozaki Reina , Sekiya Takeo , Sato Takuma , Tabuchi Masako , Miyazawa Ken , Naruse Keiko 
Published: October 2024

ABSTRACTAims/IntroductionOrthodontic treatment involves alveolar bone remodeling in response to mechanical loading, resulting in tooth movement through traction‐side bone formation and compression‐side bone resorption. However, there are conflicting reports regarding alveolar bone resorption during the orthodontic treatment of patients with diabetes.Materials and MethodsDiabetes was induced in 8‐week‐old C56BL/6J mice using streptozotocin (STZ). Four weeks after the injection of STZ, a mechanical load was applied between the first and second molars on the right side of the upper jaw using the Waldo method with orthodontic elastics in diabetic (DM) and normal (N) mice tooth movement, gene expression, osteoclast counts, alveolar bone residual volume, and bone beam structure were evaluated.ResultsThe duration until spontaneous elastic loss was significantly longer in the DM group, suggesting that tooth movement may be inhibited in the diabetic state. The number of osteoclasts at 7 days after mechanical loading and the alveolar bone resorption were both significantly lower in the DM group. The gene expression levels of vascular endothelial growth factor (VEGF), a protein related to alveolar bone remodeling, and specificity protein 1 (SP1), a transcription factor of the VEGF gene, were significantly lower in the DM group than in the N group on the compression side of mechanical loading.ConclusionsMechanical loading‐induced alveolar bone remodeling is suppressed in the diabetic state. Our results suggest that VEGF is a key molecule involved in impaired bone remodeling under mechanical loading in the diabetic state.
Association between malnutrition and adverse renal outcomes in patients with type 2 diabetes
Authors: Fujiwara Momoko , Kimura Hiroshi , Tanaka Kenichi , Saito Hirotaka , Shimabukuro Michio , Asahi Koichi , Watanabe Tsuyoshi , Kazama Junichiro James 
Published: October 2024

ABSTRACTIntroductionNutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients.Materials and MethodsThe study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end‐stage kidney disease. All‐cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis.ResultsThe median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of the renal event (HR 5.15, 95% CI 2.51–10.6) and all‐cause death (HR 2.30, 95% CI 1.20–4.42). A significant association was not observed between GNRI levels and cardiovascular events.ConclusionsWe observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes.
Mandarin Fish Ranavirus (MRV) Infection Induced Inflammation and Histologic Lesions in the Gut of Mandarin Fish
Authors: Gao Xinru , Zhang Ziye , Ma Yanping , Hao Le , Huang Wen , Liu Zhenxing , Li Yugu 
Published: October 2024

ABSTRACTMandarin fish ranavirus (MRV) is widely spread in China and causes huge economic losses to the mandarin fish (Siniperca chuatsi) aquaculture. However, the pathogenesis of MRV is still unclear. In the present study, mandarin fish were artificially infected with MRV, and then different gut compartments from diseased fish were subjected to histologic analysis by H&E staining, quantification of proinflammatory genes and MRV copies by qPCR. MRV‐MCP protein expression was assessed using indirect fluorescence assay (IFA) and immunohistochemistry. Proliferation of IgM+ B cells was evaluated by indirect fluorescence assay (IFA). Then, we found that MRV infection caused serious histologic lesions along with inflammatory cell infiltration, especially in the foregut. A significant accumulation of IgM+ B cells was detected in the foregut (~6.5‐fold) and hindgut (~3.3‐fold), respectively. The expression of inflammation‐related genes such as IL‐1β, IL‐6, IL‐8, TNF‐α, CSF1r and NCF1 was significantly upregulated in the foregut, varying from ~2.8‐fold to ~11.9‐fold. In addition, MRV exhibited foregut tropism, according to the investigation of viral loads and MCP protein expression. Overall, our findings indicated that MRV‐induced hyperinflammation in the gut eventually led to enteritis. This study provided new insights into uncovering the pathogenesis of MRV infection.
Bone labeling experiments and intraskeletal growth patterns in captive leopard geckos (Eublepharis macularius)
Authors: Schlief Sierra C. , Richman Joy M. , Brink Kirstin S. 
Published: October 2024

AbstractAn understanding of the dynamics of bone growth is key to interpreting life‐history parameters of vertebrates. In this study, we used fluorochrome labels in captive leopard geckos (Eublepharis macularius) to track bone growth and intraskeletal variability from embryonic to adult growth stages. Thirteen individuals were administered fluorochromes from pre‐hatching to 4 years of age. The left tibia, fibula, femur, humerus, radius, and ulna were examined histologically and compared for differences in the number of labels within and between individuals at each sampled growth stage, and the amount of bone growth between labels was calculated. Results suggest that limb elements had differing growth rates; the fibula grew the fastest per day on average and the femur grew the slowest per day on average. All labels administered in ovo were still present in all limb elements in adults except for the tibia, suggesting growth marks are not lost in most elements and accurate calculations of growth rates could be performed in individuals up to 3 years old. All ex ovo labels were accounted for; however, when two fluorochromes were administered 3 weeks apart, the labels could not be differentiated from each other due to the new bone not being deposited at a quantifiable level. Overall, the tibia in leopard geckos is the least reliable limb bone to use for skeletochronology and the humerus, radius, and fibula preserve the longest growth record. This research highlights that, as in other extinct and extant animals, patterns of bone growth are not consistent across reptiles. This study adds to the growing body of knowledge on growth variability in reptiles.
Relationship Between Social Isolation, Loneliness and Psychological Well‐Being in Inflammatory Bowel Disease Patients: The Mediating Role of Disease Activity Social Isolation in Inflammatory Bowel Disease
Authors: Yildirim Yasemin , Artan Yağmur , Unal Nalan Gülşen 
Published: October 2024

ABSTRACTAimTo evaluate the relationship between social isolation, loneliness and psychological well‐being in patients with inflammatory bowel disease (IBD). Additionally, we examined the mediating effect of disease activity on the relationships between social isolation, loneliness and psychological well‐being.DesignCross‐sectional descriptive study.MethodsA total of 218 participants were recruited from outpatient clinic at a university hospital in Turkey and from the community membership of the patient support group. Participants provided their socio‐demographic and disease‐related information and completed (online and paper based) the Turkish Lubben Social Network Scale‐6, the Turkish UCLA Loneliness Scale Short Form and the Turkish Psychological Well‐being Scale. The data were analysed using univariate linear regression analysis. This study adhered to the STROBE checklist for reporting.ResultsThe majority of the participants (72%) were socially isolated, and over half (54.1%) reported moderate to high levels of loneliness. Participants also had low psychological well‐being. Linear regression analysis revealed that high loneliness level and social isolation were negative predictors of psychological well‐being. The results revealed that the effect of social isolation and loneliness on psychological well‐being was mediated by disease activity.ConclusionIn line with the findings, it can be recommended to enhance social support and networks, along with regular psychological evaluation, should be integrated into the holistic care approach for IBD patients.Relevance to Clinical PracticeThe findings of this study hold significant implications for the management and support of patients with IBD, particularly within clinical settings in Turkey.Patient or Public ContributionPatients were invited to complete questionnaires. The investigators explained the study's content and purpose, and addressed any concerns during the data collection process.