bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a flipped learning course to deliver and scale molecular variant evaluation education: A quality improvement initiative
Authors: Balcom Jessica R. , Ellingson Marissa S. , Bowler Carrie A. , Richardson Darcy M. , Kruisselbrink Teresa , Thomas Brittany C. 
Published: January 2024

AbstractOver the past several decades, molecular genetic testing volumes have grown and testing has expanded from single‐gene assays to multigene panels, exome sequencing, and genome sequencing. The number of molecular genetic variants that require manual interpretation has grown simultaneously, resulting in an increased demand for education on molecular variant evaluation (MVE). To meet this growing need, a team of genetic counselors and educational experts undertook a quality improvement (QI) initiative with the objectives of assessing, standardizing, and scaling access to MVE education, without increasing instructor time to deliver the education. Using the Six Sigma define–measure–analyze–improve–control (DMAIC) framework, a flipped learning course with a series of standardized online modules was developed to deliver MVE education in an enduring and accessible format for a diverse group of learners. Outcome measures included the number of online modules developed, the number of individual learners and unique learner groups accessing MVE education, and direct instruction time required to deliver MVE education. Countermeasures to ensure maintenance of educational quality included post‐course learner satisfaction scores and performance on competency assessments. Both the total number of learners and the number of unique learner groups accessing MVE education increased, while instructor time required to deliver content per learner decreased. Learner satisfaction scores remained constant and performance on competency assessments improved. The QI initiative successfully scaled MVE education to a diverse group of learners without decreasing learner outcomes or satisfaction. The flipped learning format provides a scalable and flexible educational model for instructors and learners in a rapidly changing environment that often includes remote work and education.
Prognosis and therapy in thyroid cancer by gene signatures related to natural killer cells
Authors: Jin Zhen , Han Yadong , Zhang Jiaxin , Liu Zhao , Li Ran , Liu Zhao 
Published: January 2024

AbstractBackgroundNatural killer (NK) cells are crucial to cancer development and prognosis. However, the role of NK cell‐related genes in immunotherapy and the tumor immune microenvironment (TIME) is not well understood. This study aimed to develop reliable risk signatures associated with NK cell‐related genes for predicting thyroid cancer (THCA).MethodsThe single‐cell RNA sequencing (scRNA‐seq) data from seven THCA samples (GSE184362) and bulk‐RNA‐seq data of 502 THCA patients (TCGA‐THCA) were included. The scRNA‐seq data was analyzed using the “Seurat” R package to identify differentially expressed genes in NK cells. The clustering analysis was carried out using the R package “ConsensusClusterPlus”. The gene set variation analysis (GSVA) algorithm was applied to assess the variations in biological pathways among subtypes. The ESTIMATE algorithm was utilized to calculate the scores for stromal, immune and estimate variables. In addition, we used the single sample Gene Set Enrichment Analysis and CIBERSORT algorithms to assess the degree to which immune cells and pathways related to immunity were enriched based on the meta‐cohort. In the TCGA‐THCA cohort, the “glmnet” R package was used for the gene selection, and LASSO Cox analysis was used to construct prognostic features. The “maftools” R package was used to examine the somatic mutation landscape of THCA in both low‐ and high‐risk groups.ResultsOne‐hundred and eighty‐five NK cell marker genes were screened, and nine genes were associated with the THCA prognosis. KLF2, OSTF1 and TAPBP were finally identified and constructed a risk signature with significant prognostic value. KLF2 and OSTF1 were protective genes, and TAPBP was a risk gene. Patients at high risk had a considerably lower overall survival compared with those at low risk. Mutations in the TCGA‐THCA cohort were predominantly C > T. Increased tumor mutation burden (TMB) levels were linked to overall survival. The low‐risk H‐TMB+ group had a better prognosis, while the high‐risk L‐TMB+ group had the worst prognosis.ConclusionNatural killer cell‐related genes KLF2, OSTF1 and TAPBP were used to develop a novel prognostic risk signature, offering a new perspective on the prognosis and treatment of THCA.
A case of benign immunoglobulin D monoclonal gammopathy of undetermined significance with 26 years of follow‐up
Authors: Anderson Larry D. , Bladé Joan , Kyle Robert A. 
Published: January 2024

AbstractThe presence of a serum immunoglobulin D (IgD) monoclonal protein (M‐protein) is seen in < 1% of patients with monoclonal gammopathies and is usually indicative of a malignant plasma cell disorder. Only a few cases of well‐documented benign monoclonal gammopathy of undetermined significance (MGUS) of IgD subtype have been reported, and only 2 of those had over 5 years of follow‐up at the time they were reported. Herein we describe longer‐term follow‐up of one of those 2 patients who has subsequently passed away from unrelated causes but never developed multiple myeloma or amyloidosis after 26 years of follow‐up. Although IgD MGUS is extremely rare, this case confirms that presence of an IgD M‐Protein is not always synonymous with a malignant plasma cell process.
Tetrahydrobiopterin (BH4) treatment stabilizes tyrosine hydroxylase: Rescue of tyrosine hydroxylase deficiency phenotypes in human neurons and in a knock‐in mouse model
Authors: Jung‐KC Kunwar , Tristán‐Noguero Alba , Altankhuyag Altanchimeg , Piñol Belenguer David , Prestegård Karina S. , Fernandez‐Carasa Irene , Colini Baldeschi Arianna , Sigatulina Bondarenko Maria , García‐Cazorla Angeles , Consiglio Antonella , Martinez Aurora 
Published: January 2024

AbstractProteostatic regulation of tyrosine hydroxylase (TH), the rate‐limiting enzyme in dopamine biosynthesis, is crucial for maintaining proper brain neurotransmitter homeostasis. Variants of the TH gene are associated with tyrosine hydroxylase deficiency (THD), a rare disorder with a wide phenotypic spectrum and variable response to treatment, which affects protein stability and may lead to accelerated degradation, loss of TH function and catecholamine deficiency. In this study, we investigated the effects of the TH cofactor tetrahydrobiopterin (BH4) on the stability of TH in isolated protein and in DAn‐ differentiated from iPSCs from a human healthy subject, as well as from THD patients with the R233H variant in homozygosity (THDA) and R328W and T399M variants in heterozygosity (THDB). We report an increase in TH and dopamine levels, and an increase in the number of TH+ cells in control and THDA cells. To translate this in vitro effect, we treated with BH4 a knock‐in THD mouse model with Th variant corresponding to R233H in patients. Importantly, treatment with BH4 significantly improved motor function in these mice, as demonstrated by increased latency on the rotarod test and improved horizontal activity (catalepsy). In conclusion, our study demonstrates the stabilizing effects of BH4 on TH protein levels and function in THD neurons and mice, rescuing disease phenotypes and improving motor outcomes. These findings highlight the therapeutic potential of BH4 as a treatment option for THDA patients with specific variants and provide insights into the modulation of TH stability and its implications for THD management.
Coexisting Th1 and Th2 cytokines in patients with collagenous gastritis and implications for its pathogenesis
Authors: Liu Qingqing , Wang Yanping , Harpaz Noam 
Published: January 2024

AbstractObjectivesCollagenous gastritis (CG) is a rare cause of refractory dyspepsia and anemia that frequently affects children and young adults and whose histological hallmark is chronic mucosal inflammation with a subepithelial collagen band. The etiology remains obscure, and no established treatments exist. We investigated the pathogenesis of CG by determining the expression profiles of genes related to immunity and inflammation in index biopsies.MethodsGastric biopsies from 10 newly diagnosed patients with CG were evaluated using the NanoString nCounter assay. Gastric biopsies from 14 normal individuals served as controls. The gene expression ratios for CG versus controls were determined in pooled samples and confirmed in individual samples by quantitative reverse transcription polymerase chain reaction. The results were compared with previously reported expression data from a cohort of patients with collagenous colitis, a colonic disorder with similar morphology, including subepithelial collagen band.ResultsCG biopsies featured enhanced expression of key genes encoding both Th1 (IFNγ, TNF‐α, IL‐2, IL‐10, IL‐12A, IL‐12B, and IL‐18) and Th2 cytokines (IL‐3, IL‐4, IL‐5, IL‐6, and IL‐13). In contrast, biopsies from patients with CC exhibited upregulated Th1 cytokines only.ConclusionsWe show in this first published gene expression profiling study that CG involves simultaneous upregulation of Th1 and Th2 cytokines. This finding is unique, contrasting with other types of chronic gastritis as well as with collagenous colitis, which shares the presence of a collagen band. Involvement of Th2 immunity in CG would support further investigation of potential dietary, environmental, or allergic factors to guide future therapeutic trials.
Mass‐correlated rotational Raman spectra and the structure of furan
Authors: Rukiye Özer Begüm , Chan Lee Jong , Heo In , Schultz Thomas 
Published: January 2024

AbstractWe present mass‐correlated rotational alignment spectroscopy and the first high‐resolution rotational Raman spectra for furan. Spectra were measured with a spectral range up to 0.5 THz and a resolution down to 1.6 MHz. Spectra for 13C and 18O isotopologues were observed in their corresponding mass channels at natural abundance. Based on our data and literature constants, we performed a purely experimental structure analysis for the effective and equilibrium structures of furan. The results highlight the utility of CRASY to obtain rare isotopologue spectra without isotopically enriched samples.
A combined approach to the vibrational characterization of medieval paints on parchment: Handheld Raman spectroscopy and micro‐SORS
Authors: Vieira Márcia , Melo Maria J. , Conti Claudia , Pozzi Federica 
Published: January 2024

AbstractA careful analytical study of the paint materials used in medieval illuminated manuscripts and their respective formulations is critical to their preservation. Due to their high value and fragile nature, access to these objects is often limited. Therefore, the development of ad‐hoc methodologies allowing researchers to collect data in the least invasive way possible is an essential task in conservation science. This article shows the potential of a combined approach that complements handheld Raman spectroscopy with micro‐SORS for the characterization of medieval paints. This methodology was tested on a reference collection of mock‐up samples prepared as pure, mixture, and layered paints on parchment, based on historical information regarding paint formulations from Iberian scriptoria. Conventional Raman analysis, carried out by means of two handheld spectrometers, was found particularly effective for materials identification in pure paints and multi‐component formulations of increasing complexity. Complementing this data, micro‐SORS proved decisive in differentiating between mixture and layered paints in most mock‐ups examined, yielding detailed information about the stratigraphy of reference samples produced through the overlaying of different paints. This combined methodology may be helpful to researchers who would like to approach the vibrational characterization of paints applied onto fragile artifacts and supports in a totally non‐invasive manner.
A network analysis of Hurricane Maria–related traumatic stress and substance use among Puerto Rican youth
Authors: Vázquez Alejandro L. , Flores Cynthia M. Navarro , Feinberg Daniel K. , Gonzalez Juan Carlos , Young John , Stewart Regan W. , Orengo‐Aguayo Rosaura E. 
Published: January 2024

AbstractYouth exposed to natural disasters are at risk of developing trauma‐related symptoms as well as engaging in substance use. Although previous research has established associations between disaster‐related stressors and substance use in youth, less has focused on how symptoms of posttraumatic stress disorder (PTSD) may underpin this association. The current study used network analysis to identify specific PTSD symptoms associated with substance use following a natural disaster. Participants were 91,732 youths (Grades 3–12) from across Puerto Rico who completed a needs assessment 5–9 months after Hurricane Maria made landfall in September 2017. We examined associations between PTSD symptoms and substance use, identified clusters of symptoms and bridges between them, and explored age‐ and binary gender–related differences in associations between specific PTSD symptoms and substance use. Analyses identified two symptom communities: (a) arousal and reactivity, negative alterations in cognition and mood, and substance use, and (b) avoidance and intrusion. Broader findings suggested that substance use was most strongly associated with PTSD‐related irritability and angry outbursts among youths. Surrounding nodes explained only 4.1% of the variance in substance use, but this was higher among youths who reported not having a supportive adult, R2 = 8.5; friend, R2 = 7.9; or teacher/counselor, R2 = 7.7, in their life. The bridge symptoms of sleep disruption and physiological reactivity were identified as potentially critical intervention targets for disrupting PTSD symptom networks after a natural disaster. Implications for triaged mental health care following natural disasters and directions for future research are discussed.
Surgical Considerations in Inner Ear Gene Therapy from Human Temporal Bone Anatomy
Authors: Brown Alyssa , Zhu MengYu , Rohani Alireza , Ladak Hanif , Agrawal Sumit K. , Stankovic Konstantina M. , Welling D. Bradley 
Published: January 2024

Objective(s)Recently directed methods of inner ear drug delivery underscore the necessity for understanding critical anatomical dimensions. This study examines anatomical measurements of the human middle and inner ear relevant for inner ear drug delivery studied with three different imaging modalities.MethodsPost‐mortem human temporal bones were analyzed using human temporal bone histopathology (N = 24), micro computerized tomography (μCT; N = 4), and synchrotron radiation phase‐contrast imaging (SR‐PCI; N = 7). Nine measurements involving the oval and round windows were performed when relevant anatomical structures were visualized for subsequent age‐controlled analysis, and comparisons were made between imaging methods.ResultsCombined human temporal bone histopathology showed the mean distance to the saccule from the center of the stapes footplate (FP) was 2.07 ± 0.357 mm and the minimum distance was 1.23 mm. The mean distance from the round window membrane (RWM) to the osseous spiral lamina (OSL) was 1.75 ± 0.199 mm and the minimum distance was 1.43 mm. Instruments inserted up to 1 mm past the center of the FP are unlikely to cause saccular damage, provided there are no endolymphatic hydrops. Similarly, instruments inserted up to 1 mm through the RWM in the trajectory toward the OSL are unlikely to cause OSL damage.ConclusionThe combined analyses of inner‐ear dimensions of age‐controlled groups and imaging modalities demonstrate critical dimensions of importance to consider when inserting delivery vehicles into the human cochlea.Level of EvidenceN/A Laryngoscope, 134:2879–2888, 2024
Social Determinants of Health and Hearing Loss in U.S. Adults
Authors: O'Brien Monica , Danis David O. , Gall Emily , Woods Kelsey , Noonan Kathryn 
Published: January 2024

ObjectivesSocial determinants of health (SDH) are nonmedical, societal factors that influence health. There is limited information on the current relationship between SDH and hearing loss (HL) in the United States. This study aims to compare the odds of HL among US adults by race/ethnicity, education level, income‐to‐poverty level ratio, health insurance coverage, and health care access.Study DesignCross‐sectional study.MethodsThe 2015–2020 National Health and Nutrition Examination Survey data were analyzed to compare odds ratios (ORs) for HL, defined as pure tone average over 25 dB HL in at least one ear, by SDH categories using sample weights. Adjusted ORs were calculated using logistic regression models controlling for sex, age, race/ethnicity, education level, income‐to‐federal‐poverty level, health care insurance coverage and access, and loud noise, pesticide, and cigarette exposure.ResultsA total of 6028 participants were included. Non‐Hispanic Black participants had half the odds of HL as Non‐Hispanic White participants (OR 0.52, p < 0.05). Lower education level correlated with higher odds of HL: those without a high school diploma had double the odds of HL compared with college graduates or above (OR 2.05, 1.91, p < 0.05). The income‐to‐federal‐poverty level ratio of 1.3 to less than 2 had higher odds of HL than the 4+ group (OR 1.45, p < 0.05). Use of multiple health care locations was associated with nearly three times the odds of HL than the group using one location (OR 2.87, p < 0.05).ConclusionSDH are associated with HL. Further investigation is needed into the mechanism of disparities for targeted prevention and treatment for hearing care equity.Level of EvidenceIV Laryngoscope, 134:2848–2856, 2024
Uncovering the complex relationship between plant diversity, soil properties, and mycorrhizal inoculum potential in threatened Miombo woodlands
Authors: Kaumbu Jean‐Marc Kyalamakasa , Sene Godar , Stefani Franck , Khasa Damase P. 
Published: January 2024

AbstractArbuscular mycorrhizal fungi (AMF) are key members of soil microbial communities and play a key role in regulating ecosystem processes. However, the mutual interdependence of plants and AMF in threatened Miombo woodlands has not yet been fully elucidated. In this study, we investigated the relationship between plant ecological indicators and soil mycorrhizal inoculum potential (MIP) in the Miombo forest fallow of Haut‐Katanga, Democratic Republic of Congo, and identified plant species that positively influence soil MIP. We conducted a floristic inventory on 32 plots and collected soil cores for physicochemical and AMF characterization. Trap cultures using Crotalaria juncea seedlings were performed to determine the soil MIP. We also tested the AMF colonization status of randomly collected living roots of mature woody and dominant herbaceous species to identify explanatory variables for MIP. Our results showed that MIP was twice as high in silty clay soils (63.13%) than in clay soils (30%). Furthermore, MIP increased accordingly with the relative abundance of a group of woody and herbaceous species (e.g., Albizia adianthifolia, Baphia bequaertii, and Setaria pumila) and decreased with others (e.g., Combretum collinum, Harungana madagascariensis and Hyparrhenia diplandra). Linear regressions showed that MIP increased significantly with the specific richness of woody species identified as indicators and with the amount of annual herbs. Woody legumes with high root colonization by AMF appeared to be refuge plants, and primary AMF dispersal vectors, increasing soil MIP. This study provides baseline data that can be used to formulate ecological restoration strategies, including soil and vegetation protection.
Research on the mechanism and application of spatial credit risk contagion based on complex network model
Authors: Ma Junhai , Liu Yuxin , Zhao Li , Liang Weihua 
Published: January 2024

AbstractDue to information asymmetry, spatial distance will affect the associated credit cooperation relationship among enterprises. This paper employed the real‐world economic data to construct the entropy spatial interaction complex network model, which effectively depicts the associated credit risk among enterprises with the consideration of the influence of spatial distance and regional economic development level. Based on the calculation experiment and the Moran index, this paper reveals the spatial correlation of the credit risk contagion in each region and builds the theoretical model for spatial correlation of credit risk contagion. The research findings indicate the facts as follows. Firstly, enterprises in regions with close spatial proximity or higher level of economic development are more likely to attract enterprises from other regions for cooperation. For instance, due to the close distance between cities and more advanced economy, the eastern coastal region in China presents more intensive enterprise cooperation with other regions. Second, the analysis using the global Moran index reveals a significant spatial credit risk contagion pattern in credit defaults during 2020, attributed to the impact of the COVID‐19 pandemic. Third, the risk contagion effect of long‐distance associated credit is more complex. With the increase of the infection rate of long‐distance linked credit risk, the system will enter a chaotic state, hindering accurate long‐term prediction.
Adaptive Long‐Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4
Authors: Chen Zhongbo , Gustavsson Emil K. , Macpherson Hannah , Anderson Claire , Clarkson Chris , Rocca Clarissa , Self Eleanor , Alvarez Jerez Pilar , Scardamaglia Annarita , Pellerin David , Montgomery Kylie , Lee Jasmaine , Gagliardi Delia , Luo Huihui ,   Genomics England Research Consortium, Hardy John , Polke James , Singleton Andrew B. , Blauwendraat Cornelis , Mathews Katherine D. , Tucci Arianna , Fu Ying‐Hui , Houlden Henry , Ryten Mina , Ptáček Louis J. 
Published: January 2024

AbstractBackgroundSpinocerebellar ataxia type 4 (SCA4) is an autosomal dominant ataxia with invariable sensory neuropathy originally described in a family with Swedish ancestry residing in Utah more than 25 years ago. Despite tight linkage to the 16q22 region, the molecular diagnosis has since remained elusive.ObjectivesInspired by pathogenic structural variation implicated in other 16q‐ataxias with linkage to the same locus, we revisited the index SCA4 cases from the Utah family using novel technologies to investigate structural variation within the candidate region.MethodsWe adopted a targeted long‐read sequencing approach with adaptive sampling on the Oxford Nanopore Technologies (ONT) platform that enables the detection of segregating structural variants within a genomic region without a priori assumptions about any variant features.ResultsUsing this approach, we found a heterozygous (GGC)n repeat expansion in the last coding exon of the zinc finger homeobox 3 (ZFHX3) gene that segregates with disease, ranging between 48 and 57 GGC repeats in affected probands. This finding was replicated in a separate family with SCA4. Furthermore, the estimation of this GGC repeat size in short‐read whole genome sequencing (WGS) data of 21,836 individuals recruited to the 100,000 Genomes Project in the UK and our in‐house dataset of 11,258 exomes did not reveal any pathogenic repeats, indicating that the variant is ultrarare.ConclusionsThese findings support the utility of adaptive long‐read sequencing as a powerful tool to decipher causative structural variation in unsolved cases of inherited neurological disease. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.