bluuebunny/crossref_metadata_2025_split huggingface dataset:
An engineered leucine zipper a position mutant with an unusual three‐state unfolding pathway
Authors: Zhu Hai , Celinski Scott A. , Scholtz J. Martin , Hu James C. 
Published: July 2002

AbstractThe leucine zipper is a dimeric coiled‐coil structural motif consisting of four to six heptad repeats, designated (abcdefg)n. In the GCN4 leucine zipper, a position 16 in the third heptad is occupied by an Asn residue whereas the other a positions are Val residues. Recently, we have constructed variants of the GCN4 leucine zipper in which the a position Val residues were replaced by Ile. The folding and unfolding of the wild‐type GCN4 leucine zipper and the Val to Ile variant both adhere to a simple two‐state mechanism. In this study, another variant of the GCN4 leucine zipper was constructed by moving the single Asn residue from a position 16 to a position 9. This switch causes the thermal unfolding of the GCN4 leucine zipper to become three state. The unfolding pathway of this variant was determined by thermal denaturation, limited proteinase K digestion, and sedimentation equilibrium analysis. Our data are consistent with a model in which the variant first unfolds from its N terminus and changes the oligomerization specificity from a native dimer to a partially unfolded intermediate containing a mixture of dimers and trimers and then completely unfolds to unstructured monomers.
In vivo carbamylation and acetylation of water‐soluble human lens αB‐crystallin lysine 92
Authors: Lapko Veniamin N. , Smith David L. , Smith Jean B. 
Published: July 2002

AbstractSeveral post‐translational modifications of lysine residues of lens proteins have been implicated in cataractogenesis. In the present study, the molecular weight of an α‐crystallin isolated from the water‐soluble portion of a cataractous human eye lens indicated that it was a modified αB‐crystallin. Further analysis by mass spectrometry of tryptic digests of this modified protein showed that Lys 92 was modified and that the sample was structurally heterogeneous. Lys 92 was acetylated in one population and carbamylated in another. Although carbamylation of lens crystallins has been predicted, this is the first documentation of in vivo carbamylation of a specific site. These results are also the first documentation of in vivo lysine acetylation of αB‐crystallin. Both modifications alter the net charge on αB‐crystallin, a feature that may have significance to cataractogenesis.
Differences in Arid Region Water Values Across Sectors: A Discussion of Potential Water Market Activity and Trading Barriers in South Central Texas
Authors: Fei Chengcheng J. , McCarl Bruce A. , Thayer Anastasia W. , Vargas Aurora , Yang Yingqian 
Published: February 2025

ABSTRACTIn water‐scarce arid regions, water trading is often proposed to increase resource use efficiency. For a potential water market to function effectively, several conditions must be met, including clearly defined and limited water rights, varying water values among users, and the absence of barriers to transfer water. Conceptually, when high‐value users face water shortages due to drought or limited water rights, they may purchase or lease water rights from low‐value users. In this paper, we examine water use values across users in the arid water‐scarce region of South‐Central Texas, as a case study, using a mix of market and nonmarket valuation approaches. This mix of methodological approaches provides results based on actual purchases, comparable sales, land rental rates, source replacement, and water‐conserving investment. Our results show considerable differences among sectoral water use values, with the lowest in agriculture and the highest for municipalities, and energy fracking. These differences suggest the potential for a broader regional water market that would increase water usage efficiency. We also explore explanations for the differences, including a thorough discussion of issues involved with trading restrictions, industry characteristics, and physical geography.
A Bidirectional Mendelian Randomization Study of Tea‐Drinking Habits and Risk of Elevated Serum Uric Acid Levels
Authors: Yan Weitian , Wang Xingqiang , Peng Zining , Deng Qian , Zhu Mengyuan , Meng Fanyu , Zhao Weiqing , Zhou Weijian , Liu Nian , Wu Jingjin , Peng Jiangyun 
Published: February 2025

ABSTRACTBackgroundAlthough recent animal experiments have revealed that tea intake improves elevated serum uric acid (SUA) levels, a causal link between the consumption of different types of tea and SUA levels remains undetermined.MethodsBidirectional Mendelian randomization (MR) analysis based on genome‐wide association studies was used to assess the causal relationship between consumption of different types of tea and the risk of elevated SUA levels in European and Asian populations.ResultsForward MR analysis showed that tea intake was significantly associated with lower SUA levels (p = 0.0013). The estimated effect value (  −0.0440) suggests that for every 1‐unit increase in tea intake, there is a 0.044‐unit decrease in SUA levels. However, there is no reverse causality between SUA and tea intake (p = 0.2824). No causal relationship was found between the consumption of different types of tea and risk of elevated SUA levels (p > 0.05).ConclusionAlthough this bidirectional MR study provided evidence of a causal relationship between tea intake and SUA levels, however, due to limitations associated with the sample size and strength of instrumental variables, a definite conclusion was not possible.
Factors Associated With Hallux Valgus Progression in Patients With Rheumatoid Arthritis: Insights From Non‐Weight‐Bearing Radiographs in the KURAMA Cohort
Authors: Ikezaki Tatsuhito , Murata Koichi , Fujii Takayuki , Onishi Akira , Murakami Kosaku , Tanaka Masao , Morinobu Akio , Matsuda Shuichi 
Published: February 2025

ABSTRACTObjectivesThis longitudinal study investigated the factors associated with hallux valgus (HV) progression in patients with rheumatoid arthritis (RA).MethodsWe included 316 patients with RA who underwent foot radiography in 2015 and more than four years later. The HV angle (HVA), first‐second intermetatarsal angle (IMA), first‐fifth intermetatarsal angle (M1/M5 angle), and calcaneal pitch (CP) angle were measured. Sesamoid position on a non‐weight‐bearing radiograph was divided into seven grades with reference to the Hardy classification. Factors of HV progression were examined.ResultsDuring a mean follow‐up period of 6.1 years, HVA increased significantly. According to the grade of the sesamoid position, feet classified as grade VI or VII showed a greater change in HVA than those classified as below grade V. In feet below grade V, high disease activity, M1/M5 angle and right side were associated with the yearly increase > 1° in the HVA. For grades VI and VII, a large CP angle was correlated with greater annual changes in the HVA.ConclusionSesamoid position relates with the increase in HVA in patients with RA. Disease activity, the existence of splay foot, and the right side are significant risk factors for an HVA increase in grades I to V.
Exploration and Identification of Potential Biomarkers and Immune Cell Infiltration Analysis in Synovial Tissue of Rheumatoid Arthritis
Authors: Liu Yan , Hu Huifang , Chen Tao , Zhu Chenxi , Sun Rui , Xu Jiayi , Liu Yi , Dai Lunzhi , Zhao Yi 
Published: February 2025

ABSTRACTIntroductionRheumatoid arthritis (RA) is a prevalent autoimmune disease with synovial inflammation and hyperplasia, which can potentially cause degradation of articular cartilage, ultimately causing joint deformity, and impaired function. However, exact mechanisms underlying RA remain incompletely understood. This study seeks to uncover genomic signatures and potential biomarkers of RA, along with exploring the biological processes involved.MethodsSix microarray datasets from RA patients, osteoarthritis (OA) and healthy controls (HC) of synovial tissue were obtained from the Gene Expression Omnibus (GEO) database for integrated analysis. Differentially expressed genes (DEGs) between groups were identified by “limma” package. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. Protein–protein interaction (PPI) network was analyzed by STRING and presented by Cytoscape. Weighted gene co‐expression network analysis (WGCNA) was conducted to discover and construct the co‐expression gene modules correlated with clinical phenotype. CytoHubba and MCODE were utilized for screening hub genes. Additionally, immune cell infiltration analysis was conducted utilizing CIBERSORT algorithm. The correlation of hub genes with immune cells were examined through Pearson Correlation Analysis.ResultsThe overlapped 92 up‐regulated genes were determined between RA versus normal controls and RA versus OA, which were primarily enriched in immune response, lymphocyte activation, and chemokine signaling pathway. By integrating WGCNA, Cytohubba and MCODE algorithms, 16 hub genes were identified including CXCL13, ITK, CXCL9, CCR5, CCR7, NKG7, CCR7, and CD52. We validated the diagnostic significance of these markers in RA by qRT‐PCR. Moreover, the analysis of immune cell infiltration demonstrated a positive association between these hub genes with B cell naïve, plasma cell, T cells follicular helper, and macrophages M1. The abundance of these cells was markedly greater in RA compared to OA and normal controls.ConclusionThis research ultimately identified 5 potential diagnostic biomarkers of RA in the synovial tissue, namely NKG7, CD52, ITK, CXCL9, and GZMA. These findings have enhanced our comprehension of RA pathogenesis and identified promising diagnostic and therapeutic targets of RA.
Characterization of DNA methylation profile of the entire CpG island spanning the 5′ untranslated region to intron 1 of the Oct4/POU5F1 gene in bovine gametes, embryos, and somatic cells
Authors: Moura Amanda Oliveira , Silva Thainara Christie Ferreira , Caetano Alexandre Rodrigues , Kussano Nayara Ribeiro , Dode Margot Alves Nunes , Franco Maurício Machaim 
Published: February 2025

AbstractStem cells are undifferentiated cells that exhibit a bivalent chromatin state that determines their fate. These cells have potential applications in human and animal health and livestock production. Somatic cell nuclear transfer or cloning is currently being used to produce genetically edited animals. A highly differentiated genome is the main obstacle to correcting epigenetic reprogramming by enucleated oocytes during cloning. Activation of pluripotency genes in the somatic genome is a promising strategy to contribute to more efficient epigenetic reprogramming, improving this technique. Recently, epigenome editing has emerged as a new generation of clustered regularly interspaced short palindromic repeats–clustered regularly interspaced short palindromic repeats‐associated protein 9 technology with the aim of modifying the cellular epigenome to turn genes on or off without modifying DNA. Here, we characterize the DNA methylation profile of the CpG island spanning the 5′ untranslated region to intron 1 of the bovine octamer‐binding transcription factor (Oct4) gene in gametes, embryos, and fibroblasts. DNA methylation patterns were categorized into three levels: low (0%–20%), moderate (21%–50%), and high (51%–100%). Sperm and embryos showed a hypomethylation pattern, whereas oocytes exhibited a hypo‐ to moderate methylation pattern. Fetal and adult skin fibroblasts were hypomethylated and moderately methylated, respectively. These results are essential for future studies aimed at manipulating the expression of Oct4. Thus, epigenome editing can be used to turn on the Oct4 in somatic cells to generate induced pluripotent stem cells. This strategy could potentially convert a fully differentiated cell into a cell with certain degree of pluripotency, facilitating nuclear reprogramming by the enucleated oocyte and improving cloning success rates.
Tracking visual outcomes – Follow‐up on patients born preterm with childhood‐onset visual impairment
Authors: Al‐Abaiji Hajer A. , Nissen Kamilla Rothe , Slidsborg Carina , La Cour Morten , Kessel Line 
Published: February 2025

AbstractPurposePreterm birth is associated with a risk of ocular complications. The primary aim of the study was to evaluate the main cause of visual impairment (VI) in a cohort of preterm born patients who had childhood‐onset VI. The association between health‐related quality of life (HRQoL) and age, cause—and severity of VI and impairment type was assessed.MethodsIn Denmark, patients <18 years with VI are enrolled at the National Danish Registry of Children with Visual Impairment (NDRCVI). Patients born preterm and enrolled at NDRCVI at any time between 1988 and 2020 were invited for a follow‐up regardless of current age. Examinations performed were visual acuity (VA), refraction, Goldmann visual fields, ocular biometry and posterior segment imaging. The three main outcomes were VA sorted by VI severity (mild, moderate, severe and blind), a score for HRQoL (HUI3) and the main cause of VI.ResultsThirty‐two preterm‐born patients participated in the study with a median age of 28 years at examination (range 8–43). ROP was the main cause of VI in 15 patients (47%) followed by CVI in eight patients (25%). Increasing age at assessment had a significantly negative impact on the HRQoL‐score, when unadjusted for type of impairments. HRQoL was significantly lower in patients with combined impairments compared to isolated VI (p = 0.003).ConclusionROP and CVI were the most common causes of VI. The HRQoL was significantly lower when VI was combined with other impairments in contrast to isolated VI. Reducing cerebral damage in preterm born children is likely to enhance both HRQoL and visual function.
A Review of Screening Guidelines for Hypoglycaemia in Infants Born Small for Gestational Age Showed Numerous Differences and Few Certainties
Authors: Remaschi Giulia , Dani Carlo 
Published: February 2025

ABSTRACTAimDifferent hypoglycaemia screening guidelines for infants born small for gestational age (SGA) are applied throughout the world. This narrative review analysed the published guidelines and evaluated the characteristic features of hypoglycaemia in SGA infants to assess the relevance of the issue.MethodsPubMed and the Cochrane Database of Systematic Reviews were reviewed for papers regarding hypoglycaemia and hypoglycaemia screening guidelines in term and near‐term SGA infants. We also searched government‐related websites and national healthcare institution websites for guidelines.ResultsNumerous differences among guidelines were found. The American Academy of Pediatrics and the Pediatric Endocrine Society do not specify which SGA infants need screening. Other guidelines suggest screening infants with birth weight < 10th percentile, while still others < 2nd percentile. Depending on the growth curves, the SGA population may change. The hypoglycaemia cut‐off value was another relevant variance. The duration of glucose level checks varies from the first 4–24 h of life. The reported incidence of hypoglycaemia was 12%–52%. The timing of hypoglycaemia onset was 2–6 h of life. Specific risk factors for hypoglycaemia in SGA infants were found.ConclusionNumerous differences were found in the hypoglycaemia guidelines for SGA infants, and further studies are needed to address strong and uniform guidance.
During Three Decades Prenatal Diagnoses of Differences in Sex Development Increased and Gonadectomy Rates Declined
Authors: Chaime Amit Eben , Phillip Moshe , Ben‐Meir David , de Vries Liat 
Published: February 2025

ABSTRACTAimThe therapeutic approach to differences of sex development (DSD) has changed over recent decades. We aimed to describe the evolution of clinical diagnoses of DSD in children attending a tertiary paediatric centre.MethodsThis retrospective observational study compared diagnoses and management, before and after the introduction of consensus guidelines for DSD in 2006.ResultsThe cohort included 87 patients with 46, XY (78.4%), 15 with 46, XX (13.5%) and 9 with sex chromosomal DSD (8.1%). Gonadectomy rates were 27.9%, 6.6% and 66.6% for the respective groups. The mean age at presentation was younger among those with 46, XY than with 46, XX (0.5 ± 2.5 vs. 6.8 ± 8.1 years, p = 0.007) and a higher proportion presented by age one year (93.1% vs. 60.0%, p = 0.001). During 1990–2006, 44 children were diagnosed, and during 2007–2019, 67 children. Prenatal diagnosis increased from 4.5% to 25.4% (p = 0.004). Smaller proportions in the later than earlier period underwent gonadectomy (19.4% vs. 40.9%, p = 0.017) and sex reassignment (1.5% vs. 13.6%, p < 0.02).ConclusionOver the three‐decade period, the rate of prenatal diagnosis increased and the rates of gonadectomy and sex reassignment declined. These findings reflect a shift towards earlier, individualised multidisciplinary care, which was facilitated by advanced diagnostics.
The Awakening of the Newborn Human Infant and the Emergence of Consciousness
Authors: Lagercrantz Hugo 
Published: February 2025

ABSTRACTConsciousness develops gradually in the womb and after birth, rather than being an all or none phenomenon. A newborn infant is aroused and wakes up at birth, due to the enormous sensory stimulation and stress that it undergoes during the transition from an aquatic environment to air. Its first breaths activate the locus coeruleus, as indicated by the large pupils of the newborn. The infant seems to be aware of its body and can recognise its mother's facial expressions, voice and smell. A default mode network matures soon after birth which appears to keep the brain in a conscious state. Thus the newborn infant is probably conscious, albeit at a low level. The foetus also shows some signs of being conscious after about 24 weeks of gestation, although it is mainly asleep in the womb and less aware of its environment. Before that stage, the nerves from the primary somatosensory, visual and auditory areas are not yet connected with the site of consciousness in the cerebral cortex.
Ability grouping in German secondary schools: The effect of non‐academic track schools on the development of Math competencies
Authors: Herrmann Sonja , Bach Katharina M. 
Published: February 2025

AbstractBackgroundDifferences in competence gains between academic and non‐academic track schools are often attributed to selection effects based on students' primary school performance and socioeconomic status (SES). However, how the competencies of comparable students (in terms of school performance and social background) at different tracks develop is often neglected.AimsWe investigated whether comparable students diverge in their math competencies due to attending different types of secondary schools, contributing to the ongoing debate on whether inaccurate stratification may lead to disadvantages.MethodsUsing data from the National Education Panel Study (Kindergarten Cohort SC2, N = 4180), we examined students' competence development from the fourth to seventh grade.We employed a quasi‐experimental design (propensity score weighting, PSW) comparing similarly capable students at academic and non‐academic school tracks to make causal inferences. The outcome variable was students' math competence in seventh grade. PSW used fourth‐grade competency measures in math and reading and other variables such as sex, migration background, SES, class composition, special educational needs, school grades and school location.ResultsResults revealed a significant average treatment effect on the treated, indicating that comparable students attending non‐academic track schools show lower math performance than those at academic track schools.ConclusionNon‐academic tracks seem to hinder the full development of students' competencies. We conclude that the effects of preconditions like the students' SES, ability and aspirations on competence development are lower than assumed and that school learning environments should be given greater importance. We discuss practical solutions and provide suggestions for future research.
Adoption and social identity loss: Insights from adults adopted through Ireland's mother and baby homes
Authors: Moroney Dearbhla , O'Donnell Aisling , O'Connor Mary , Muldoon Orla T. 
Published: February 2025

AbstractA central issue in adoption research is understanding why some individuals adapt to their adoption experience while others face considerable difficulties. The social identity approach (SIA) offers a valuable framework for examining this. Recent research has increasingly shown that identifying with social groups can protect and promote well‐being. However, in the context of adoption, certain groups may also present challenges or become sources of strain. The present study seeks to understand how social identities shape individuals' adoption experiences. Semi‐structured interviews (N = 16) with adults who were adopted through Mother and Baby Homes in Ireland were analysed using reflexive thematic analysis. The analysis produced two interrelated themes: (1) ‘Adopted’ as a social identity, which explores how participants' ‘adopted’ status itself constitutes a significant social identity, leading to experiences of marginalization and exclusion and (2) Adoption as social identity loss, which describes how participants face contested membership and compromised belonging within important social groups. Both themes illustrate how the process of adoption can result in social identity loss. Discussion of this analysis considers the consequences of social identity change for adoption adjustment. These findings expand the theoretical application of the SIA, in the context of adoption.
Analysis of Two Neuroanatomical Subtypes of Parkinson's Disease and Their Motor Progression Based on Semi‐Supervised Machine Learning
Authors: Zhou Hao , Wu Yuqing , Chen Shuoying , Xing Yi , Ren Jingru , Liu Weiguo 
Published: February 2025

ABSTRACTBackgroundThe high heterogeneity of Parkinson's disease (PD) hinders personalized interventions. Brain structure reflects damage and neuroplasticity and is one of the biological bases of symptomatology. Subtyping PD in the framework of brain structure helps in the prediction of disease trajectories and optimizes treatment strategies.MethodsThe study included a total of 283 de novo PD and 141 healthy controls (HC). Structural heterogeneity between PD and HC was compared, and patients were classified using Heterogeneity through Discriminative Analysis. Gray matter volume (GMV), clinical symptoms, and substantia nigra free water (SNFW) among all subtypes were compared. These subtypes were followed for an average of 2.5 years to monitor motor impairment.ResultsEarly PD patients possessed higher GMV heterogeneity than HC, and two subtypes based on GMV patterns were identified. Subtype 1 showed widespread GMV reductions, while subtype 2 had an increased volume in the basal ganglia and parts of the cortex. Subtype 1 had more severe motor and non‐motor symptoms, as well as higher posterior SNFW. The whole‐brain GMV in the PD group was negatively correlated with posterior SNFW; basal ganglia volume in subtype 1 was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS)‐III scores, whereas no linear correlation was found in subtype 2. The UPDRS‐III progression rate was higher in subtype 1 than in subtype 2 (2.52 vs 0.92 points/year).ConclusionThe heterogeneity of PD patients reflected the changes in their brain structure. The identification of these changes helps the classification of patients into different subtypes, additionally supported by clinical manifestations and SNFW, with consequent benefits for clinical consultancy and precision medicine.