bluuebunny/crossref_metadata_2025_split huggingface dataset:
From phenotype to mechanism: Prenatal spectrum of NKAP mutation‐related disorder and its pathogenesis inducing congenital heart disease
Authors: Xu Xiayuan , Gao Chengcheng , Ye Fenglei , Peng Aohui , Xu Jianbo , Jin Keqin , Zhang Jun , Ye Yun , Yang Yanfen , Zhang Xuan , Shen Shuangshuang , Jin Fan 
Published: April 2024

AbstractNKAP mutations are associated with Hackmann‐Di Donato‐type X‐linked syndromic intellectual developmental disorder (MRXSHD, MIM: #301039). Here, we elucidate the potential prenatal manifestation of NKAP mutation‐associated disorder for the first time, alongside revealing the relationship between NKAP mutations and congenital heart defect (CHD) in the Chinese population. An NKAP mutation (NM_024528.4: c.988C>T, p.Arg330Cys) was identified in two foetuses presenting with CHD. Subsequent mechanistic exploration revealed a marked downregulation of NKAP transcription within HEK293T cells transfected with NKAP p.R330C. However, no significant change was observed at the protein level. Moreover, the mutation led to a dysregulation in the transcription of genes associated with cardiac morphogenesis, such as DHRS3, DNAH11 and JAG1. Additionally, our research determined that NKAP p.R330C affected Nkap protein intra‐nuclear distribution, and binding with Hdac3. Summarily, our study strengthens NKAP mutations as a cause of CHD and prompts the reclassification of NKAP p.R330C as likely pathogenic, thereby establishing a prospective prenatal phenotypic spectrum that provides new insight into the prenatal diagnosis of CHD. Our findings also provide evidence of NKAP p.R330C pathogenicity and demonstrate the potential mechanism by which p.R330C dysregulates cardiac developmental gene transcription by altering Nkap intra‐nuclear distribution and obstructing the interaction between Nkap and Hdac3, thereby leading to CHD.
Patient‐reported outcome measurements in facial skin surgery and a comparison between Mohs micrographic surgery and conventional excisions
Authors: Marsidi N. , Ottevanger R. , Demir Y. E. , van Beugen S. , Goeman J. J. , Genders R. E. 
Published: April 2024

AbstractBackgroundKnowledge of the psychosocial impact of facial skin surgery on patients can help improve counselling strategies.ObjectivesThe objective was to measure the psychological impact of facial skin cancer surgery on patients over a 1‐year period. Secondary objective was to measure the difference between Mohs micrographic surgery (MMS) and conventional excision (CE) on these parameters.MethodsThis observational survey study was conducted between March 2019 and July 2020. Patients who had facial skin surgery using MMS or CE were selected. Five surveys were conducted on four timepoints (preoperative, 1 week, 3 months and 1 year post‐operative) measuring the quality of life, perceived stigmatization, body image, satisfaction with facial appearance and psychosocial distress.ResultsA total of 228 patients (MMS 154 patients, CE 74 patients) were included for the analysis. Scores for quality of life did not significantly change, in the year after surgery (PCS‐12 mean 50.5, SD 9.3 and MCS‐12 50.6, SD 9.4); however, stigmatization (F (3, 235,39) 7,26, p < 0.01, d = −0.07), body image concerns (F (3, 198,28) = 3.75, p < 0.01, d = −0.14), satisfaction with facial appearance (F (3, 205,18) = 10.74, p < 0.01, d = 0.43) and psychosocial distress (F (3, 208,69) = 9.26, p < 0.01, d = −0.15) did change over time. The use of MMS or CE did not significantly affect outcome scores after 1 year.ConclusionsPatients receiving facial skin cancer surgery exhibited low scores for perceived stigmatization and body image concerns. Their quality of life was not statistically influenced by facial surgery, and their satisfaction with their facial appearance and psychosocial distress even improved after 1 year. The results suggest that the surgical treatment type (MMS or CE) does not influence the outcome. The overall results can help in counselling strategies to improve expectations for patients receiving facial surgery.
CircSOD2: Disruption of intestinal mucosal barrier function in ulcerative colitis by regulating the miR‐378g/Snail1 axis
Authors: Ye Guannan , Zhang Jiayi , Peng Jin , Zhou Zhen , Wang Weining , Yao Si 
Published: April 2024

AbstractBackground and AimCircular RNA (circRNA) has been found to mediate ulcerative colitis (UC) progression by regulating intestinal mucosal barrier function. However, the role of circSOD2 in UC process and its underlying molecular mechanism still need to be further elucidated.MethodsLipopolysaccharide (LPS)‐induced Caco2 cells were used to mimic UC cell models. CircSOD2, miR‐378g, and Snail1 levels were determined by quantitative real‐time PCR. Cell viability was detected using MTT assay, and inflammatory cytokine levels were measured using ELISA. The intestinal mucosal barrier function was evaluated by testing transepithelial electrical resistance and fluorescein isothiocyanate (FITC)‐dextran permeability. Snail1 and tight junction‐related markers (Zo‐1 and Claudin2) protein levels were examined using western blot. The interaction between miR‐378g and circSOD2 or Snail1 was confirmed by dual‐luciferase reporter assay. Dextran sulfate sodium (DSS) was used to induce UC rat models in vivo.ResultsCircSOD2 was overexpressed in UC patients, and its knockdown significantly increased cell viability, transepithelial electrical resistance, and tight junction‐related protein expression, while reduced inflammation cytokine levels and the permeability of FITC‐dextran in LPS‐induced Caco2 cells. In terms of mechanism, circSOD2 sponged miR‐378g to positively regulate Snail1 expression. MiR‐378g inhibitor reversed the effect of circSOD2 knockdown on intestinal mucosal barrier injury and Snail1 expression in LPS‐induced Caco2 cells. In DSS‐induced UC rat models, circSOD2 knockdown also could repair the intestinal mucosal barrier injury through regulating miR‐378g/Snail1 axis.ConclusionCircSOD2 could destroy intestinal mucosal barrier function in LPS‐induced Caco2 cells and DSS‐induced UC rats by miR‐378g/Snail1 axis.
Development and validation of a questionnaire to assess health‐related quality‐of‐life in cats with hyperthyroidism
Authors: Blunschi Fabienne , Schofield Imogen , Muthmann Sofie , Bauer Natali B. , Hazuchova Katarina 
Published: April 2024

AbstractBackgroundHealth‐related quality‐of‐life (HRQoL) assessment tools are becoming increasingly important for the assessment of diseases in veterinary medicine.ObjectivesTo develop a tool to assess the HRQoL of hyperthyroid cats and their owners.AnimalsCats with hyperthyroidism (n = 229) and without hyperthyroidism (n = 322).MethodsCross‐sectional study design. A preliminary list of 28 questions relating to the HRQoL of hyperthyroid cats and the influence their cat's disease might have on owners was created. Each question consisted of 2 subquestions: (1) “how often does the item apply”; (2) “how strongly does the item affect HRQoL.” The questionnaire was refined based on statistical analysis, including Mann‐Whitney‐U tests on each item, comparing the results from cats with and without hyperthyroidism. Internal consistency and reliability of the questions were measured by Cronbach's alpha (α). P < .05 was considered significant.ResultsOverall, 25/28 questions were retained within the final HRQoL tool, which had an excellent internal consistency (α = .92). The tool produced a score between 0 and 382 (lower scores meaning better HRQoL). The median HRQoL score was 87.5 (range, 2‐348) for cats with hyperthyroidism, and 27 (range, 0‐249) for cats without (P < .001), suggesting the HRQoL was poorer in hyperthyroid cats.Conclusions and Clinical ImportanceThis validated HRQoL tool is useful to reliably quantify the influence of hyperthyroidism on the quality‐of‐life of affected cats and their owners. In the future, it could be considered of assistance in the clinical assessment of cats with hyperthyroidism.
A novel four‐gene‐based inheritance model explains gradations of nakedness in cotton (Gossypium hirsutum L.)
Authors: Revanasiddayya  , Patil Shreekant S. , Nidagundi Jayaprakash Mohan , Maralappanavar Manjula S. , Patil S. B. , Kariyannanavar Prashant 
Published: April 2024

AbstractIn crop improvement, delineating inheritance pattern of a character guides a plant breeder to choose appropriate breeding procedure, which enables ease of improving phenotypic expression of the traits. To deduce the inheritance pattern of naked seed or fuzzless character, four parental lines involving two purely naked seed types (DHN‐1 and DHN‐10), one partial naked seed type (SP46CC) and one fully fuzzy type (OSB415) were used to develop three different types of crosses, namely, naked × naked seed type cross (N × N), partial naked × naked seed type cross (PN × N) and fuzzy × naked seed type cross (F × N). We observed that naked trait segregates in the ratio of 11 naked: 5 partial naked in N × N cross, 22 naked: 42 partial naked in PN × N cross and 22 naked: 42 partial naked: 192 fuzzy in F × N cross. Our study reports a novel four‐gene model to understand inheritance nature of naked seed character where the presence of single basic dominant fuzzy gene negates the effect of genes controlling nakedness resulting fuzzy phenotype irrespective of the number of partial fuzzyness/nakedness imparting alleles. This indicates that nakedness is recessive to fuzzyness. Based on our results, we infer observing gradations of nakedness on seeds depends on the presence of number of partial fuzzyness imparting alleles, which led to a conclusion that the trait exhibited dose‐dependent expression with one basic gene for fuzziness.
Epigenomic mechanism regulating the quality and ripeness of apple fruit with differing harvest maturity
Authors: Wang Jing , Wang Jiahe , Li Yu , Lv Yongqian , Zhao Juan , Li Hao , Zhang Bo , Zhang Mengsheng , Tian Jianwen , Li Xiaolong , Xing Libo 
Published: April 2024

AbstractHarvest maturity significantly affects the quality of apple fruit in post‐harvest storage process. Although the regulatory mechanisms underlying fruit ripening have been studied, the associated epigenetic modifications remain unclear. Thus, we compared the DNA methylation changes and the transcriptional responses of mature fruit (MF) and immature fruit (NF). There were significant correlations between DNA methylation and gene expression. Moreover, the sugar contents (sucrose, glucose, and fructose) were higher in MF than in NF, whereas the opposite pattern was detected for the starch content. The expression‐level differences were due to DNA methylations and ultimately resulted in diverse fruit textures and ripeness. Furthermore, the higher ethylene, auxin, and abscisic acid levels in MF than in NF, which influenced the fruit texture and ripening, were associated with multiple differentially expressed genes in hormone synthesis, signaling, and response pathways (ACS, ACO, ZEP, NCED, and ABA2) that were regulated by DNA methylations. Multiple transcription factor genes involved in regulating fruit ripening and quality via changes in DNA methylation were identified, including MIKCC‐type MADS‐box genes and fruit ripening‐related genes (NAP, SPL, WRKY, and NAC genes). These findings reflect the diversity in the epigenetic regulation of gene expression and may be relevant for elucidating the epigenetic regulatory mechanism underlying the ripening and quality of apple fruit with differing harvest maturity.
Application of the unified theory of behavior to strengthen sexual health discussions between providers and young patients in the United States
Authors: Lanier Yzette , Rivera‐Cash Dennis , Lavarin Claudine , Goldstein Alena , Cantu Luke , Phung Baomi , Guilamo‐Ramos Vincent , Sutton Madeline 
Published: April 2024

AbstractContextSexual health discussions between healthcare providers and adolescent and young adult patients are an important strategy for addressing and improving sexual health. However, healthcare providers often do not engage in comprehensive sexual health discussions with young patients during routine clinical visits.MethodsWe propose the use of a conceptual model, the Unified Theory of Behavior (UTB), as a tool that can aid healthcare providers in facilitating more comprehensive sexual health conversations with young patients.ResultsWe present clinical scenarios on how healthcare providers can use the UTB with existing sexual health assessments during routine, clinical visits with their patients.ConclusionsUsing the UTB may be one effective tool to aid healthcare providers in initiating sexual health discussions and facilitating more comprehensive sexual health conversations with adolescent and young adult patients during routine clinical visits and sexual and reproductive health‐focused visits.
Mangiferin improves early porcine embryonic development by reducing oxidative stress
Authors: Ji He‐Wei , Wang Chao‐Rui , Yuan Xiu‐Wen , Wang Jing , Wang Lin , Cao Qi‐Long , Li Ying‐Hua , Xu Yong‐Nan , Kim Nam‐Hyung 
Published: April 2024

AbstractMangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti‐lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 μM). The addition of 0.1 μM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation‐related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria‐related (TFAM, PGC1α) genes was upregulated. In contrast, the expression of apoptosis‐related (CAS3, BAX) and autophagy‐related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress‐related genes.
Advances in lung transplantation: 60 years on
Authors: Paraskeva Miranda A. , Snell Gregory I. 
Published: April 2024

AbstractLung transplantation is a well‐established treatment for advanced lung disease, improving survival and quality of life. Over the last 60 years all aspects of lung transplantation have evolved significantly and exponential growth in transplant volume. This has been particularly evident over the last decade with a substantial increase in lung transplant numbers as a result of innovations in donor utilization procurement, including the use donation after circulatory death and ex‐vivo lung perfusion organs. Donor lungs have proved to be surprisingly robust, and therefore the donor pool is actually larger than previously thought. Parallel to this, lung transplant outcomes have continued to improve with improved acute management as well as microbiological and immunological insights and innovations. The management of lung transplant recipients continues to be complex and heavily dependent on a tertiary care multidisciplinary paradigm. Whilst long term outcomes continue to be limited by chronic lung allograft dysfunction improvements in diagnostics, mechanistic understanding and evolutions in treatment paradigms have all contributed to a median survival that in some centres approaches 10 years. As ongoing studies build on developing novel approaches to diagnosis and treatment of transplant complications and improvements in donor utilization more individuals will have the opportunity to benefit from lung transplantation. As has always been the case, early referral for transplant consideration is important to achieve best results.
The institutionalization of “serial personalization” in Argentina's Peronist Party, 1983–2023
Authors: Malamud Andres , Marsteintredet Leiv 
Published: April 2024

AbstractObjectiveThe purpose of this article is to explain how Peronism, an allegedly personalist party, has managed to institutionalize its internal power struggles and its succession procedures since democratization in 1983.MethodsThe authors employ the common conceptual framework developed for this special issue. Evidence is drawn from public media, scholarly sources, and participant observation. A two‐tier approach to party adaptation is developed to distinguish the capacity to adjust to electoral challenges from the capacity to adjust to governmental challenges.Results and conclusionThe authors develop the concept of “serial personalization” to describe an informally routinized feature by which middle‐rank and subnational leaders transfer their loyalty from one personalistic leader to another as long as he or she delivers the best possible electoral performance and, when in office, fiscal transferences.
Enhancing soil properties through sustainable agronomic practices reduced the occurrence of kiwifruit vine decline syndrome
Authors: Sofo Adriano , Dichio Bartolomeo , Elshafie Hazem S. , Camele Ippolito , Calabritto Maria , Tomasi Isabella , Mastroleo Marco , Xylogiannis Evangelos , D'Ippolito Ilaria , Mininni Alba N. 
Published: April 2024

AbstractKiwifruit vine decline syndrome (KVDS) is an emerging challenge related to various factors, including water stagnation, soil compaction, root hypoxia, imbalanced soil redox potential, soil nutrient imbalance and fungal pathogens, yet its definitive causes remain unconfirmed. This study compared soils and roots of healthy plants (CTRL group) and plants affected by KVDS (KVDS group) at a kiwifruit orchard (Actinidia chinensis cv. ‘Zesy002’) in Sermoneta (Lazio region), Italy. Our findings indicate that soil redox potential, a parameter related to soil oxidation, and soil macroporosity were significantly lower in the KVDS soils. The water table was also found to be higher in the KVDS block of the orchard, demonstrating a higher soil water content. This suggests less aeration and more water content in KVDS‐affected soils compared to the control. Root analyses showed that KVDS led to browning and decomposition of rhizodermis, decay of the central stele, detachment of the cortex, reduced cell size and the presence of starch granules in the parenchyma, with significant variations in root morphometric parameters. To mitigate KVDS, sustainable agronomic practices, including precision irrigation, green manure, compost addition and water drainage root pruning, were carried out on some KVDS‐symptomatic vines (SUST group). Molecular analyses revealed the presence of 10 fungal species from treated root plants, with Paraphaeosphaeria michotii, Fusarium oxysporum and Ilyonectria vredenhoekensis being frequently isolated from symptomatic KVDS‐affected plants but less from SUST plants. Also, Beauveria bassiana and Bacillus amyloliquefaciens, showed an effect against I. vredenhoekensis and P. michotii, and may be suitable candidates as biocontrol agents. The adoption of sustainable agronomic practices resulted in significantly more healthy plants (46% increase) by the end of the trial, demonstrating that a sustainable soil use and water management at kiwifruit orchards can mitigate KVDS through restoration of natural growth conditions.
Epigenetic dissection of human blood group genes reveals regulatory elements and detailed characteristics of KEL and four other loci
Authors: Wu Ping Chun , McGowan Eunike C. , Lee Yan Quan , Ghosh Sudip , Hansson Jenny , Olsson Martin L. 
Published: April 2024

AbstractBackgroundBlood typing is essential for safe transfusions and is performed serologically or genetically. Genotyping predominantly focuses on coding regions, but non‐coding variants may affect gene regulation, as demonstrated in the ABO, FY and XG systems. To uncover regulatory loci, we expanded a recently developed bioinformatics pipeline for discovery of non‐coding variants by including additional epigenetic datasets.MethodsMultiple datasets including ChIP‐seq with erythroid transcription factors (TFs), histone modifications (H3K27ac, H3K4me1), and chromatin accessibility (ATAC‐seq) were analyzed. Candidate regulatory regions were investigated for activity (luciferase assays) and TF binding (electrophoretic mobility shift assay, EMSA, and mass spectrometry, MS).ResultsIn total, 814 potential regulatory sites in 47 blood‐group‐related genes were identified where one or more erythroid TFs bound. Enhancer candidates in CR1, EMP3, ABCB6, and ABCC4 indicated by ATAC‐seq, histone markers, and co‐occupancy of 4 TFs (GATA1/KLF1/RUNX1/NFE2) were investigated but only CR1 and ABCC4 showed increased transcription. Co‐occupancy of GATA1 and KLF1 was observed in the KEL promoter, previously reported to contain GATA1 and Sp1 sites. TF binding energy scores decreased when three naturally occurring variants were introduced into GATA1 and KLF1 motifs. Two of three GATA1 sites and the KLF1 site were confirmed functionally. EMSA and MS demonstrated increased GATA1 and KLF1 binding to the wild‐type compared to variant motifs.DiscussionThis combined bioinformatics and experimental approach revealed multiple candidate regulatory regions and predicted TF co‐occupancy sites. The KEL promoter was characterized in detail, indicating that two adjacent GATA1 and KLF1 motifs are most crucial for transcription.
Evaluation of clinical response and prognostic factors in canine multicentric lymphoma treated with first rescue therapy
Authors: Blaxill John E. , Bennett Peter F. 
Published: April 2024

AbstractDespite an initial strong response in most dogs with multicentric lymphoma treated with chemotherapy, relapse remains common. There is no clearly superior first rescue protocol described either for resistant or relapsed canine multicentric lymphoma. The objectives of this study were to assess clinical response and outcomes for canine multicentric lymphoma treated with first rescue protocols. The secondary objective was to assess prognostic variables for dogs undergoing these protocols. This was a bi‐institutional retrospective cohort study. Two hundred and sixty‐five dogs were treated with first rescue chemotherapy, including anthracycline‐based combination chemotherapy (CHOP‐like, n = 50), nitrosourea alkylating agent‐rich chemotherapy (n = 45), anthracycline‐based or related compound chemotherapy (n = 34), or nitrosourea single‐agent chemotherapy (n = 136). The overall median progression free survival time of first rescue protocol was 56.0 days (0–455 days). Important prognostic factors identified for first rescue protocol included the attainment of a complete response to the first rescue chemotherapy (p < .001), the use of a CHOP‐like first rescue protocol (p = .009), duration of first remission (HR 0.997, p = .028), and if prednisolone was included in the first rescue protocol (HR 0.41, p = .003). Adverse events (AE) were common, with 81.1% of dogs experiencing at least one AE during first rescue chemotherapy. This study highlights the need for improved first rescue therapies to provide durable remission in canine resistant or relapsed lymphoma.