bluuebunny/crossref_metadata_2025 huggingface dataset:
Table S3 from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer
Authors: Gupta Santosh , Halabi Susan , Yang Qian , Roy Akash , Tubbs Alisa , Gore Yamini , George Daniel J. , Nanus David M. , Antonarakis Emmanuel S. , Danila Daniel C. , Szmulewitz Russell Z. , Wenstrup Richard , Armstrong Andrew J.
Published: April 2023

A. Overall Survival outcomes and B. Progression Free Survival outcomes utilizing multivariate analysis for PSMA positive CTCs, adjusting on prior treatment, risk score, CTC enumeration, comparting 3 CTC + groups with the reference group being CTC 0.
Figure S4 from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer
Authors: Gupta Santosh , Halabi Susan , Yang Qian , Roy Akash , Tubbs Alisa , Gore Yamini , George Daniel J. , Nanus David M. , Antonarakis Emmanuel S. , Danila Daniel C. , Szmulewitz Russell Z. , Wenstrup Richard , Armstrong Andrew J.
Published: April 2023

Percent PSMA expression positivity (PSMA+CTC x 100/ Traditional CTC) across PSMA+ Neuroendocrine Phenotype (NE) - and PSMA+ NE+ baseline (A) and progression (B) samples.
Supplementary Table 1 from UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression
Authors: Zhao Rong , Liu Yan , Wang Ziwei , Zhang Jun , Zhang Wei , Zhou Xing , Tsedendorj Sevjid , Enkhtur Amarsanaa , Feng Dilu , Wang Hongbo
Published: April 2023

Table S1. Primers for qPCR
Figure S7 from UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression
Authors: Zhao Rong , Liu Yan , Wang Ziwei , Zhang Jun , Zhang Wei , Zhou Xing , Tsedendorj Sevjid , Enkhtur Amarsanaa , Feng Dilu , Wang Hongbo
Published: April 2023

Figure S7
Supplementary Figures and Legends, Supplementary Tables from Downregulation of BASP1 Promotes Temozolomide Resistance in Gliomas via Epigenetic Activation of the FBXO32/NF-κB/MGMT Axis
Authors: Liao Xinyi , Li Ziwen , Zheng Haiqing , Qian Wanying , Zhang Shuxia , Chen Suwen , Li Xincheng , Tang Miaoling , Xu Yingru , Yu Ruyuan , Li Man , Song Libing , Li Jun
Published: April 2023

S1. BASP1 downregulation is associated with poor prognosis in glioma patients.S2. Low expression of BASP1 is associated with poor prognosis in CGGA dataset.S3. Dysregulation of BASP1 alters chemoresistance of glioma cells to TMZ treatment in vitro.S4. BASP1 dysregulation has no effect on the rate of glioma cell growth in vivo.S5. Dysregulation of BASP1 alters chemoresistance to TMZ treatment in glioma cells in vivo.S6. BASP1 silencing activates NF-κB signaling in glioma cells.S7. FBXO32 expression correlates with NF-κB signaling.S8. BXO32 expression positively correlates with MGMT expression.S9. FBXO32 is associated with poor prognosis of glioma patients.S10. WDR5/MLL upregulates FBXO32 epigenetically.S11. Combined OICR-9429 sensitizes BASP1-silenced glioma cells to TMZ in vivo.Supplementary Table S1. Clinicopathological characteristics of studied patients and BASP1 expression in gliomas.Supplementary Table S2. Correlation between the clinicopathological features and expression.Supplementary Table S3. Univariate and multivariate analysis of different prognostic parameters in glioma patients by Cox-regression analysis.Supplementary Table S4. Primers and Oligonucleotides used in this study.
Figure S4 from UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression
Authors: Zhao Rong , Liu Yan , Wang Ziwei , Zhang Jun , Zhang Wei , Zhou Xing , Tsedendorj Sevjid , Enkhtur Amarsanaa , Feng Dilu , Wang Hongbo
Published: April 2023

Figure S4
Figure S3 from UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression
Authors: Zhao Rong , Liu Yan , Wang Ziwei , Zhang Jun , Zhang Wei , Zhou Xing , Tsedendorj Sevjid , Enkhtur Amarsanaa , Feng Dilu , Wang Hongbo
Published: April 2023

Figure S3
Figure S5 from Interdependence of SS18-SSX–driven YAP1 and β-Catenin Activation in Synovial Sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: April 2023

Figure S5 shows that there is no interdependency between YAP1/TAZ and β-catenin activation in control cell lines.
Figure S1 from UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression
Authors: Zhao Rong , Liu Yan , Wang Ziwei , Zhang Jun , Zhang Wei , Zhou Xing , Tsedendorj Sevjid , Enkhtur Amarsanaa , Feng Dilu , Wang Hongbo
Published: April 2023

Figure S1
Table S2 from USP10 Regulates ZEB1 Ubiquitination and Protein Stability to Inhibit ZEB1-Mediated Colorectal Cancer Metastasis
Authors: Sun Lei , Yu Jia , Guinney Justin , Qin Bo , Sinicrope Frank A.
Published: April 2023

Human colon cancer cohorts with tumors subjected to comprehensive gene expression profiling for determination of consensus molecular subtypes (CMS)[33].
Data from FOXA1 Reprogramming Dictates Retinoid X Receptor Response in ESR1-Mutant Breast Cancer
Authors: Wu Yang , Li Zheqi , Wedn Abdalla M. , Casey Allison N. , Brown Daniel , Rao Shalini V. , Omarjee Soleilmane , Hooda Jagmohan , Carroll Jason S. , Gertz Jason , Atkinson Jennifer M. , Lee Adrian V. , Oesterreich Steffi
Published: April 2023

Abstract
Estrogen receptor alpha (ER/ESR1) mutations occur in 30% to 40% of endocrine resistant ER-positive (ER+) breast cancer. Forkhead box A1 (FOXA1) is a key pioneer factor mediating ER–chromatin interactions and endocrine response in ER+ breast cancer, but its role in ESR1-mutant breast cancer remains unclear. Our previous FOXA1 chromatin immunoprecipitation sequencing (ChIP-seq) identified a large portion of redistributed binding sites in T47D genome-edited Y537S and D538G ESR1–mutant cells. Here, we further integrated FOXA1 genomic binding profile with the isogenic ER cistrome, accessible genome, and transcriptome data of T47D cell model. FOXA1 redistribution was significantly associated with transcriptomic alterations caused by ESR1 mutations. Furthermore, in ESR1-mutant cells, FOXA1-binding sites less frequently overlapped with ER, and differential gene expression was less associated with the canonical FOXA1–ER axis. Motif analysis revealed a unique enrichment of retinoid X receptor (RXR) motifs in FOXA1-binding sites of ESR1-mutant cells. Consistently, ESR1-mutant cells were more sensitive to growth stimulation with the RXR agonist LG268. The mutant-specific response was dependent on two RXR isoforms, RXR-α and RXR-β, with a stronger dependency on the latter. In addition, T3, the agonist of thyroid receptor (TR) also showed a similar growth-promoting effect in ESR1-mutant cells. Importantly, RXR antagonist HX531 blocked growth of ESR1-mutant cells and a patient-derived xenograft (PDX)-derived organoid with an ESR1 D538G mutation. Collectively, our data support the evidence for a stronger RXR response associated with FOXA1 reprograming in ESR1-mutant cells, suggesting development of therapeutic strategies targeting RXR pathways in breast tumors with ESR1 mutation.
Implications:
It provides comprehensive characterization of the role of FOXA1 in ESR1-mutant breast cancer and potential therapeutic strategy through blocking RXR activation.
Supplementary Data from HDAC3 Inhibition Promotes Antitumor Immunity by Enhancing CXCL10-Mediated Chemotaxis and Recruiting of Immune Cells
Authors: Li Lili , Hao Shumin , Gao Meiling , Liu Junxiao , Xu Xin , Huang Jianfei , Cheng Genhong , Yang Heng
Published: April 2023

Supplementary Fig. S1-S9 Table S1-S2
Supplementary Table S2 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration
Authors: Nóbrega-Pereira Sandrina , Santos Francisco , Santos Miguel Oliveira , Serafim Teresa L. , Patrícia Lopes Ana , Coutinho Diogo , Carvalho Filipa S. , Domingues Rosário M. , Domingues Pedro , Bernardes de Jesus Bruno , Morais Vanessa A , Dias Sérgio
Published: April 2023

Fatty acid profile in relative content (%). Qualitative analysis was calculated by dividing each raw area by the sum of total raw areas. Dash (‘-‘) represents lipid species that were not identified in the sample. Legend: CTR (control), ETO (etomoxir, 100 µM).
Supplementary Figure S8 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration
Authors: Nóbrega-Pereira Sandrina , Santos Francisco , Santos Miguel Oliveira , Serafim Teresa L. , Patrícia Lopes Ana , Coutinho Diogo , Carvalho Filipa S. , Domingues Rosário M. , Domingues Pedro , Bernardes de Jesus Bruno , Morais Vanessa A , Dias Sérgio
Published: April 2023

Uncropped membranes relative to the western blot for Drp1, Mfn1, Mfn2 and b-ACTIN proteins displayed in Fig. 2J
Supplementary Figure S5 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration
Authors: Nóbrega-Pereira Sandrina , Santos Francisco , Santos Miguel Oliveira , Serafim Teresa L. , Patrícia Lopes Ana , Coutinho Diogo , Carvalho Filipa S. , Domingues Rosário M. , Domingues Pedro , Bernardes de Jesus Bruno , Morais Vanessa A , Dias Sérgio
Published: April 2023

LDL-induced migratory behavior of TNBC cells relies on fatty acid transport into the mitochondria. Related to Fig. 5
Supplementary Figure S3 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration
Authors: Nóbrega-Pereira Sandrina , Santos Francisco , Santos Miguel Oliveira , Serafim Teresa L. , Patrícia Lopes Ana , Coutinho Diogo , Carvalho Filipa S. , Domingues Rosário M. , Domingues Pedro , Bernardes de Jesus Bruno , Morais Vanessa A , Dias Sérgio
Published: April 2023

LDL-induced breast cancer cell migration is mediated by the fatty acid transporter CD36. Related to Fig. 3
Supplementary Figure S2 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration
Authors: Nóbrega-Pereira Sandrina , Santos Francisco , Santos Miguel Oliveira , Serafim Teresa L. , Patrícia Lopes Ana , Coutinho Diogo , Carvalho Filipa S. , Domingues Rosário M. , Domingues Pedro , Bernardes de Jesus Bruno , Morais Vanessa A , Dias Sérgio
Published: April 2023

LDL exposure induces mitochondrial network spread distribution and destabilized cristae in migrating breast cancer cells. Related to Fig. 2
Supplementary Figure S5 from Structurally Complex Osteosarcoma Genomes Exhibit Limited Heterogeneity within Individual Tumors and across Evolutionary Time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew V. , Cam Maren , Gross Amy C. , Raphael Benjamin J. , Roberts Ryan D.
Published: April 2023

Fraction of altered genome density plots
Supplementary Figure S4 from Structurally Complex Osteosarcoma Genomes Exhibit Limited Heterogeneity within Individual Tumors and across Evolutionary Time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew V. , Cam Maren , Gross Amy C. , Raphael Benjamin J. , Roberts Ryan D.
Published: April 2023

Proportion of identically assigned SCNAs between samples
Data from Structurally Complex Osteosarcoma Genomes Exhibit Limited Heterogeneity within Individual Tumors and across Evolutionary Time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew V. , Cam Maren , Gross Amy C. , Raphael Benjamin J. , Roberts Ryan D.
Published: April 2023

Osteosarcoma is an aggressive malignancy characterized by high genomic complexity. Identification of few recurrent mutations in protein coding genes suggests that somatic copy-number aberrations (SCNA) are the genetic drivers of disease. Models around genomic instability conflict—it is unclear whether osteosarcomas result from pervasive ongoing clonal evolution with continuous optimization of the fitness landscape or an early catastrophic event followed by stable maintenance of an abnormal genome. We address this question by investigating SCNAs in >12,000 tumor cells obtained from human osteosarcomas using single-cell DNA sequencing, with a degree of precision and accuracy not possible when inferring single-cell states using bulk sequencing. Using the CHISEL algorithm, we inferred allele- and haplotype-specific SCNAs from this whole-genome single-cell DNA sequencing data. Surprisingly, despite extensive structural complexity, these tumors exhibit a high degree of cell-cell homogeneity with little subclonal diversification. Longitudinal analysis of patient samples obtained at distant therapeutic timepoints (diagnosis, relapse) demonstrated remarkable conservation of SCNA profiles over tumor evolution. Phylogenetic analysis suggests that the majority of SCNAs were acquired early in the oncogenic process, with relatively few structure-altering events arising in response to therapy or during adaptation to growth in metastatic tissues. These data further support the emerging hypothesis that early catastrophic events, rather than sustained genomic instability, give rise to structural complexity, which is then preserved over long periods of tumor developmental time.
Significance:
Chromosomally complex tumors are often described as genomically unstable. However, determining whether complexity arises from remote time-limited events that give rise to structural alterations or a progressive accumulation of structural events in persistently unstable tumors has implications for diagnosis, biomarker assessment, mechanisms of treatment resistance, and represents a conceptual advance in our understanding of intratumoral heterogeneity and tumor evolution.
Expanding the p.(Arg85Trp) Variant-Specific Phenotype of HNF4A: Features of Glycogen Storage Disease, Liver Cirrhosis, Impaired Mitochondrial Function, and Glomerular Changes
Authors: Grassi Mara , Laubscher Bernard , Pandey Amit V. , Tschumi Sibylle , Graber Franziska , Schaller André , Janner Marco , Aeberli Daniel , Hewer Ekkehard , Nuoffer Jean-Marc , Gautschi Matthias
Published: April 2023

Introduction: The p.(Arg85Trp) variant-specific phenotype of hepatocyte nuclear factor 4 alpha shows a complex clinical picture affecting three different organ systems and their corresponding metabolisms. Little is known about the molecular mechanisms involved and their relationship with the diverse symptoms seen in the context of this specific variant. Here, we present data of a new patient that expand the clinical phenotype, suggesting possible disease mechanisms. Case Presentation: Clinical data were extracted from the patient’s charts. The liver, kidney, and muscle were analyzed with routine histology and electron microscopy. Mitochondrial function was assessed by respirometric analyses and enzymatic activity assays. Structure and sequence analyses of this specific variant were investigated by in silico analyses. Our patient showed the known features of the variant-specific phenotype, including macrosomia, congenital hyperinsulinism, transient hepatomegaly, and renal Fanconi syndrome. In addition to that, she showed liver cirrhosis, chronic kidney failure, and altered mitochondrial morphology and function. The clinical and biochemical phenotype had features of a new type of glycogen storage disease. Discussion: This case expands the p.(Arg85Trp) variant-specific phenotype. Possible pathomechanistic explanations for the documented multiorgan involvement and changes of symptoms and signs during development of this ultra-rare but instructive disorder are discussed.
Circulating Tumor DNA Testing Overcomes Limitations of Comprehensive Genomic Profiling from Tumor Tissue
Authors: Kumar Anivarya , Green Michelle , Thacker Julie , Jeck William Richard , Strickler John H.
Published: April 2023

“Liquid biopsy” is an established technique for examining circulating tumor DNA (ctDNA) from a routine blood draw and detecting actionable biomarkers. Nonetheless, ctDNA testing is rarely utilized for patients with newly diagnosed metastatic colorectal cancer (CRC). We report a case in which ctDNA testing uncovered an actionable biomarker that was not detected by comprehensive genomic profiling of tumor tissue. An 81-year-old woman with a remote history of non-Hodgkin’s lymphoma presented with primary masses in the ascending colon and sigmoid colon. The ascending colon and sigmoid colon tumors were classified as microsatellite stable (MSS) and mismatch repair proficient (pMMR), and both ctDNA and tissue next-generation sequencing (NGS) from the ascending colon mass were ordered. Because tissue NGS results indicated that the ascending colon tumor was MSS, palliative 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy was started. However, the ctDNA NGS results that arrived after the start of FOLFOX found high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR) disease with a serine/threonine-protein kinase B-Raf (BRAFV600E) mutation. To treat both her MSS/pMMR ascending colon and sigmoid colon tumors and MSI-H/dMMR metastatic disease, the immunotherapy nivolumab was added to FOLFOX. After 8 months of combined nivolumab and chemotherapy, the patient’s metastatic disease had a complete clinical response. This case highlights the complementary role of ctDNA testing for biomarker identification. By performing simultaneous ctDNA testing at the time of diagnosis, an actionable biomarker was discovered that significantly altered this patient’s prognosis and treatment options. Orthogonal testing of key molecular alterations offers significant advantages for identifying actionable biomarkers and improving management of metastatic CRC.
In utero Exposure to Valproic Acid throughout Pregnancy Causes Phenotypes of Autism in Offspring Mice
Authors: Mitsuhashi Takayuki , Hattori Satoko , Fujimura Kimino , Shibata Shinsuke , Miyakawa Tsuyoshi , Takahashi Takao
Published: April 2023

Valproic acid (VPA) is an antiepileptic drug that inhibits the epileptic activity of neurons mainly by inhibiting sodium channels and GABA transaminase. VPA is also known to inhibit histone deacetylases, which epigenetically modify the cell proliferation/differentiation characteristics of stem/progenitor cells within developing tissues. Recent clinical studies in humans have indicated that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in offspring; we have previously reported that low-dose VPA exposure in utero throughout pregnancy increases the production of projection neurons from neuronal stem/progenitor cells that are distributed in the superficial neocortical layers of the fetal brain. In the present study, we found that in utero VPA-exposed mice exhibited abnormal social interaction, changes in cognitive function, hypersensitivity to pain/heat, and impaired locomotor activity, all of which are characteristic symptoms of autism spectrum disorder in humans. Taken together, our findings indicate that VPA exposure in utero throughout pregnancy alters higher brain function and predisposes individuals to phenotypes that resemble autism and intellectual disability. Furthermore, these symptoms are likely to be due to neocortical dysgenesis that was caused by an increased number of projection neurons in specific layers of the neocortex.
Construction of an Explanatory Model for Quality of Life in Outpatients with Ulcerative Colitis
Authors: Takahashi Miho , Nunotani Maya , Aoyama Nobuo
Published: April 2023

Introduction: To date, no studies have reported explanatory models of health-related quality of life (HRQoL) in patients with ulcerative colitis. Therefore, this study aimed to examine HRQoL and its related factors in outpatients with ulcerative colitis to construct an explanatory model. Methods: We conducted a cross-sectional survey at a clinic in Japan. The HRQoL was evaluated using the 32-item Inflammatory Bowel Disease Questionnaire. We extracted explanatory variables of HRQoL from demographic, physical, psychological, and social factors reported in previous studies and created a predictive explanatory model. The relationship between explanatory variables and the questionnaire total score was examined using Spearman’s rank correlation coefficient, the Mann-Whitney test, or the Kruskal-Wallis test. We conducted multiple regression and path analyses to examine the effect of explanatory variables on the total score. Results: We included 203 patients. Variables that were associated with the total score were the partial Mayo score (r = −0.451), treatment side effects (p = 0.004), the Hospital Anxiety and Depression Scale-Anxiety score (r = −0.678), the Hospital Anxiety and Depression Scale-Depression score (r = −0.528), and the availability of an advisor during difficult times (p = 0.001). The model included the partial Mayo score, treatment side effects, the Hospital Anxiety and Depression Scale-Anxiety score, and the availability of an advisor during difficult times as explanatory variables of the total score that showed the best goodness-of-fit (adjusted R2 = 0.597). The anxiety score exerted the greatest negative effect on the questionnaire total score (β = −0.586), followed by the partial Mayo score (β = −0.373), treatment side effects (β = 0.121), and availability of an advisor during difficult times (β = −0.101). Conclusion: Psychological symptoms exerted the strongest direct effect on HRQoL in outpatients with ulcerative colitis and mediated the relationship between social support and HRQoL. Nurses should listen carefully to the concerns and anxieties of patients to ensure that a social support system is provided by leveraging multidisciplinary collaborations.
Targeting Wnt-ß-Catenin-FOSL Signaling Ameliorates Right Ventricular Remodeling
Authors: Nayakanti Sreenath Reddy , Friedrich Aleksandra , Sarode Poonam , Jafari Leili , Maroli Giovanni , Boehm Mario , Bourgeois Alice , Grobs Yann , Khassafi Fatemeh , Kuenne Carsten , Guenther Stefan , Dabral Swati , Wilhelm Jochen , Weiss Astrid , Wietelmann Astrid , Kojonazarov Baktybek , Janssen Wiebke , Looso Mario , de Man Frances , Provencher Steeve , Tello Khodr , Seeger Werner , Bonnet Sebastien , Savai Rajkumar , Schermuly Ralph T. , Pullamsetti Soni Savai
Published: April 2023

Background:

The ability of the right ventricle (RV) to adapt to an increased pressure afterload determines survival in patients with pulmonary arterial hypertension. At present, there are no specific treatments available to prevent RV failure, except for heart/lung transplantation. The wingless/int-1 (Wnt) signaling pathway plays an important role in the development of the RV and may also be implicated in adult cardiac remodeling.

Methods:

Molecular, biochemical, and pharmacological approaches were used both in vitro and in vivo to investigate the role of Wnt signaling in RV remodeling.

Results:

Wnt/β-catenin signaling molecules are upregulated in RV of patients with pulmonary arterial hypertension and animal models of RV overload (pulmonary artery banding-induced and monocrotaline rat models). Activation of Wnt/β-catenin signaling leads to RV remodeling via transcriptional activation of FOSL1 and FOSL2 (FOS proto-oncogene [FOS] like 1/2, AP-1 [activator protein 1] transcription factor subunit). Immunohistochemical analysis of pulmonary artery banding -exposed BAT-Gal (β-catenin-activated transgene driving expression of nuclear β-galactosidase) reporter mice RVs exhibited an increase in β-catenin expression compared with their respective controls. Genetic inhibition of β-catenin, FOSL1/2, or WNT3A stimulation of RV fibroblasts significantly reduced collagen synthesis and other remodeling genes. Importantly, pharmacological inhibition of Wnt signaling using inhibitor of PORCN (porcupine O-acyltransferase), LGKK-974 attenuated fibrosis and cardiac hypertrophy leading to improvement in RV function in both, pulmonary artery banding - and monocrotaline-induced RV overload.

Conclusions:

Wnt- β-Catenin-FOSL signaling is centrally involved in the hypertrophic RV response to increased afterload, offering novel targets for therapeutic interference with RV failure in pulmonary hypertension.
Associations of Renal Function Trajectories and Long‐Term Cardiovascular Risks Among a Population Without Chronic Kidney Disease
Authors: Zhai Yuan‐Sheng , Cheng Yun‐Jiu , Deng Hai‐Wei , Li Jie , Peng Longyun , Gao Xiuren
Published: April 2023

Background

The longitudinal trajectories of renal function have been associated with cardiovascular events in patients with chronic kidney disease (CKD). However, the change pattern of renal function in those without CKD has not yet been reported. We aim to explore patterns of renal function change in a non‐CKD population and its associated risks with cardiovascular outcomes.

Methods and Results

The present study analyzed data from 4 prospective cohorts and was restricted to participants without baseline CKD. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, chronic heart failure, stroke, and cardiovascular deaths. We used a group‐based trajectory model to identify latent groups and analyzed the associated risk with Cox regression models. The complete dates of this study were June 1, 2020, through January 1, 2021. The final sample comprised 23 760 participants (mean age, 58.63 [9.12] years, 10 618 men, and 17 799 White participants). During 20.56 years follow‐up, 8328 (35.05%) first major adverse cardiovascular events happened. Four trajectories in estimated glomerular renal function and 3 patterns of CKD progression were identified. Compared with subjects assigned to class I trajectory (high to mildly decreased group), the adjusted hazard ratios of major adverse cardiovascular events for class II (normal to mildly decreased group), class III (normal to moderately decreased group), and class IV (mildly to severely decreased group) were 1.11 (95% CI, 1.01–1.23), 1.27 (95% CI, 1.14–1.40), and 1.56 (95% CI, 1.38–1.77), respectively. Likewise, participants assigned to the slow and rapid progression groups had elevated HRs for major adverse cardiovascular events (1.75 [95% CI, 1.39–2.21] and 2.19 [95% CI, 1.68–2.86], respectively) when compared with the stable group. Findings were generally consistent in stratification analysis, but significant interaction effects by age and smoking status were detected.

Conclusions

In this study, we identified unique trajectory groups for renal function. These findings may signal an underlying high‐risk population and inspire future studies on individualized risk management.
Kimura disease as an uncommon cause of persistent hypereosinophilia: a diagnostic challenge
Authors: Merino Anna , Laguna Javier , Rodríguez-García María , Molina Angel
Published: April 2023

Kimura disease (KD) is an unusual inflammatory disease of unknown etiology. Despite being described many years ago, KD might cause diagnostic difficulty or be confused with other conditions. Here, we present a 33-year-old Filipino woman who was referred to our hospital for evaluation of persistent eosinophilia and intense pruritus. Blood analysis and peripheral blood smear review showed high eosinophil counts (3.8 x109/L, 40%) that did not show morphological abnormalities. Besides, high serum IgE concentration was detected (33,528 kU/L). Serological tests were positive for Toxocara canis and treatment with albendazol was initiated. Nevertheless, increased eosinophil counts were still present after several months, alongside with high serum IgE concentrations and intense pruritus. During her follow-up, an inguinal adenopathy was detected. The biopsy revealed lymphoid hyperplasia with reactive germinal centers and massive eosinophil infiltration. Proteinaceous deposits of eosinophilic material were also observed. All these findings, together with peripheral blood eosinophilia and high IgE concentrations, confirmed the diagnosis of KD. The diagnosis of KD should be considered in the differential diagnosis of long-standing unexplained eosinophilia in association with high IgE concentrations, pruritus and lymphadenopathies.
Gabor and Non-Gabor Neural Representations Are Shared between Visual Perception and Mental Imagery
Authors: Huang Yingying , Pollick Frank , Liu Ming , Zhang Delong
Published: April 2023

Visual perception and mental imagery have been shown to share a hierarchical topological visual structure of neural representation, despite the existence of dissociation of neural substrate between them in function and structure. However, we have limited knowledge about how the visual hierarchical cortex is involved in visual perception and visual imagery in a unique and shared fashion. In this study, a data set including a visual perception and an imagery experiment with human participants was used to train 2 types of voxel-wise encoding models. These models were based on Gabor features and voxel activity patterns of high-level visual cortex (i.e., fusiform face area, parahippocampal place area, and lateral occipital complex) to predict activity in the early visual cortex (EVC, i.e., V1, V2, V3) during perception, and then tested with respect to the generalization of these models to mental imagery. Our results showed that during perception and imagery, activities in the EVC could be independently predicted by the Gabor features and activity of high-level visual cortex via voxel-wise encoding models, which suggested that perception and imagery might share neural representation in the EVC. We further found Gabor-specific and non-Gabor-specific patterns of neural response to stimuli in the EVC, which were shared by perception and imagery. These findings provide insight into the mechanisms of how visual perception and imagery share representation in the EVC.
Correlations between Visual Temporal Resolution and Individual Alpha Peak Frequency: Evidence that Internal and Measurement Noise Drive Null Findings
Authors: Deodato Michele , Melcher David
Published: April 2023

The brain organizes the continuous flow of sensory input by parsing it into discrete events. In the case of two flashes separated by a brief ISI, for example, perception may be of a single flash or two distinct flashes, depending on the ISI but also on the speed of processing. A number of studies have reported evidence that participants with a higher EEG peak alpha frequency are able to detect the presence of two flashes separated by short intervals, whereas those with slower alpha report only one flash. Other studies have not found this correlation. We investigated potential factors that might mask the relationship between individual alpha frequency and visual perception. We recorded resting-state EEG from a large sample of participants (n = 50) and measured the temporal resolution of visual perception with the two-flash fusion task. We found that individual alpha frequency over posterior channels predicted the two-flash fusion threshold, in line with previous studies, but this correlation was significant only when taking into account the steepness of the psychophysical curve of the two-flash task. Participants with a relatively shallow psychophysical curve, likely reflecting high sensory and/or decision noise, failed to show this relationship. These findings replicate previous reports of a correlation between alpha frequency and visual temporal resolution, while also suggesting that an explanation of two-flash fusion performance that neglects the role of internal noise might be insufficient to account for all individual differences.
Stimulus Onset Asynchrony Affects Weighting-related Event-related Spectral Power in Self-motion Perception
Authors: Townsend Ben , Legere Joey K. , v. Mohrenschildt Martin , Shedden Judith M.
Published: April 2023

Self-motion perception relies primarily on the integration of the visual, vestibular, proprioceptive, and somatosensory systems. There is a gap in understanding how a temporal lag between visual and vestibular motion cues affects visual–vestibular weighting during self-motion perception. The beta band is an index of visual–vestibular weighting, in that robust beta event-related synchronization (ERS) is associated with visual weighting bias, and robust beta event-related desynchronization is associated with vestibular weighting bias. The present study examined modulation of event-related spectral power during a heading judgment task in which participants attended to either visual (optic flow) or physical (inertial cues stimulating the vestibular, proprioceptive and somatosensory systems) motion cues from a motion simulator mounted on a MOOG Stewart Platform. The temporal lag between the onset of visual and physical motion cues was manipulated to produce three lag conditions: simultaneous onset, visual before physical motion onset, and physical before visual motion onset. There were two main findings. First, we demonstrated that when the attended motion cue was presented before an ignored cue, the power of beta associated with the attended modality was greater than when visual–vestibular cues were presented simultaneously or when the ignored cue was presented first. This was the case for beta ERS when the visual-motion cue was attended to, and beta event-related desynchronization when the physical-motion cue was attended to. Second, we tested whether the power of feature-binding gamma ERS (demonstrated in audiovisual and visual–tactile integration studies) increased when the visual–vestibular cues were presented simultaneously versus with temporal asynchrony. We did not observe an increase in gamma ERS when cues were presented simultaneously, suggesting that electrophysiological markers of visual–vestibular binding differ from markers of audiovisual and visual–tactile integration. All event-related spectral power reported in this study were generated from dipoles projecting from the left and right motor areas, based on the results of Measure Projection Analysis.
Towards a Genealogy of Thomas Kuhn’s Semantics
Authors: Melogno Pablo , Giri Leandro
Published: April 2023

This paper explores Thomas Kuhn’s intellectual history by examining sources that have been understudied so far: the Lowell Lectures of 1951 (The Quest for Physical Theory) and the hitherto unpublished Notre Dame Lectures of 1980. The analysis of these texts aims to reconstruct Kuhn’s development of a semantics that can account for scientific progress. This analysis will show that the alleged “linguistic turn” attributed to the author is actually a renewed interest in problems that existed well before publishing The Structure of Scientific Revolutions.
Dealing with Molecular Complexity. Atomistic Computer Simulations and Scientific Explanation
Authors: Schweer Julie , Elstner Marcus
Published: April 2023

Explanation is commonly considered one of the central goals of science. Although computer simulations have become an important tool in many scientific areas, various philosophical concerns indicate that their explanatory power requires further scrutiny. We examine a case study in which atomistic simulations have been used to examine the factors responsible for the transport selectivity of certain channel proteins located at cell membranes. By elucidating how precisely atomistic simulations helped scientists draw inferences about the molecular system under investigation, we respond to some concerns regarding their explanatory power. We argue that atomistic simulations can be tools for managing molecular complexity and for systematically assessing how the occurrence of the explanandum is sensitive to a range of factors.
Oecumene in het Midden-Oosten
Authors: Teule Herman G.B.
Published: April 2023

Ecumenism in the Middle-East Same historical investigations (eighth-thirteenth centuries)

The author discusses, for the period of roughly the Abbasid Caliphate, three different mentalities regarding ecumenism. Firstly, the attitude that the absolute norm for truth can be found only in one’s own ecclesiastical community; other Christians can only be regarded as heretics. No attempt is made to understand their theology. Secondly, the attitude that on the basis of rational arguments one tries to enter into a respectful dialogue with other Christians, be it that ultimately truth is still thought to be present only in the own community. Thirdly, the relativization of one’s traditional theological terminology, which opens the way to finding validity also in the theological expression of ‘other’ Christians.

The third attitude is mainly, but not exclusively, found in Christian Arabic texts. It seems a logical, further step in the process that Christians in the Middle East, from the ninth century onwards, made extensive use of a philosophical method and argumentation rather than that it would be due to a Muslim environment.
A Technical Overview of the North Carolina ECONet
Authors: Saia Sheila M. , Heuser Sean P. , Neill Myleigh D. , LaForce IV William A. , McGuire John A. , Dello Kathie D.
Published: April 2023

Regional weather networks—also referred to as mesonets—are imperative for filling in the spatial and temporal data gaps between nationally supported weather stations. The North Carolina Environment and Climate Observing Network (ECONet) fills this regional role; it is a mesoscale network of 44 (as of 2023) automated stations collecting 12 environmental variables every minute across North Carolina. Measured variables include air temperature, precipitation, relative humidity, barometric pressure, wind speed, wind direction, total solar radiation, photosynthetically active solar radiation, soil temperature, soil moisture, leaf wetness index, and black globe temperature. All data undergo quality control procedures and are made freely available to the public via data portals hosted by the State Climate Office of North Carolina at North Carolina State University. This paper provides a technical overview of ECONet, including a description of the siting criteria, station maintenance procedures, data quality control procedures, and data availability. We also summarize unique aspects of ECONet data collection as well as innovative research and applications that rely on ECONet data. ECONet data are used by many sectors including, but not limited to, emergency management, natural resources management, public health, agriculture, forestry, science education, outdoor recreation, and research. ECONet data and data-powered applications offer valuable insights to local, regional, and federal partners, yet opportunities to expand ECONet research and applications remain.

Significance Statement

This paper explains the ongoing and emerging impacts of a statewide weather station network called the North Carolina Environment and Climate Observing Network (ECONet). ECONet consists of 44 (as of 2023) automated stations located across the state. Each station collects 12 environmental variables every minute. ECONet data and data-powered applications offer valuable insights to local, regional, and federal partners. There are many opportunities to expand ECONet-based research and applications.
A Simple Method for Estimating Horizontal Diffusivity
Authors: Olivé Abelló Anna , Pelegrí Josep L. , Machín Francisco
Published: April 2023

A common dilemma for oceanographers is the choice of horizontal diffusivity. There is no single answer as we could argue that diffusion depends precisely on those processes that cannot be sampled or modeled. Here we propose the radial offset by diffusion (ROD) method as a simple model-dependent approach for estimating these coefficients, and show its application for the southwestern South Atlantic. The method compares actual displacements of field drifters with numerical trajectory predictions. The observed–predicted differences in radial positions (radial offsets), which respond to diffusive motions not captured by the numerical model, are reproduced with a one-dimensional radial-diffusive solution through a proper selection of the diffusion coefficient. The method is tested at eight depths, from the sea surface down to 2000 m, using several drifter datasets and the Parcels software applied to the GLORYS12v1 (1/12° daily) velocity outputs. In all cases the radial offsets show Gaussian distributions that are well reproduced by the radial diffusive solution. Maximum diffusivities of 4630–4980 m2 s−1 happen in the upper 200 m of the water column and minimum values of 1080–1270 m2 s−1 occur between 1400 and 2000 m. The 15-m diffusivity is fairly constant in latitude (3850–5270 m2 s−1), but the 1000-m diffusivity decreases from 1640 to 1820 m2 s−1 north of the Polar Front to 530 m2 s−1 south of the Southern Boundary. A comparison with other diffusivity studies validates the good adequacy of the ROD method for numerical and field applications.
Evaluating the Impacts of COSMIC-2 GNSS RO Bending Angle Assimilation on Atlantic Hurricane Forecasts Using the HWRF Model
Authors: Miller William J. , Chen Yong , Ho Shu-Peng , Shao Xi
Published: April 2023

This study evaluates the impact of assimilating Global Navigation Satellite System (GNSS) radio occultation (RO) bending angles from Formosa Satellite Mission-7/Constellation Observing System for Meteorology, Ionosphere, and Climate-2 (COSMIC-2) receiver satellites on Hurricane Weather Research and Forecasting (HWRF) Model tropical cyclone (TC) forecasts. Launched in June 2019, the COSMIC-2 mission provides significantly higher tropics data coverage compared to its predecessor COSMIC constellation. GNSS RO measurements yield information about atmospheric pressure, temperature, and water vapor profiles. HWRF is cycled with and without COSMIC-2 bending angle data assimilation for six 2020 Atlantic hurricane cases. COSMIC-2 assimilation has little impact on HWRF track forecasts, consistent with HWRF’s design limiting cycled data assimilation impacts on surrounding large-scale flows; however, COSMIC-2 assimilation results in a statistically significant ∼8%–12% mean absolute forecast error reduction in minimum central sea level pressure for t = 36-, 54-, 60-, and 108–120-h lead times. Forecasts initialized from analyses assimilating COSMIC-2 observations also have a 1%–4% smaller 600–700-hPa specific humidity (SPFH) root-mean-squared deviation compared to radiosondes and dropwindsondes for most lead times. While not all HWRF intensity forecasts benefit from COSMIC-2 assimilation, a few show notable improvement. For example, assimilating two COSMIC-2 profiles within the inner core of developing Hurricane Hanna (2020) increases 800-hPa SPFH by up to 1 g kg−1 locally, helping to correct a dry bias. The forecast initialized from this analysis better captures Hanna’s observed intensification rate, likely because its moister inner core facilitates development of persistent deep convection near the TC center, where diabatic heating is more efficiently converted to cyclonic wind kinetic energy.

Significance Statement

Tropical cyclone (TC) intensification can be strongly sensitive to the lower-to-midtropospheric water vapor distribution near the storm. The COSMIC-2 GNSS radio occultation (RO) receiver satellite mission provides denser spatial coverage of atmospheric water vapor and temperature profiles over the tropics compared to other GNSS RO observation platforms. Herein, using six 2020 Atlantic TC cases, we evaluate the impacts of assimilating COSMIC-2 RO bending angles into a regional forecast model that already assimilates clear-sky satellite radiances. It is shown that COSMIC-2 assimilation yields a modest ∼10% intensity forecast skill improvement for several lead times, although more substantial intensity forecast improvement is found for a few forecasts where the COSMIC-2 observation assimilation helps correct a lower-to-midtropospheric water vapor bias.
The Impact of Tropical SST Biases on the S2S Precipitation Forecast Skill over the Contiguous United States in the UFS Global Coupled Model
Authors: Bai Hedanqiu , Li Bin , Mehra Avichal , Meixner Jessica , Moorthi Shrinivas , Ray Sulagna , Stefanova Lydia , Wang Jiande , Wang Jun , Worthen Denise , Yang Fanglin , Stan Cristiana
Published: April 2023

This work investigates the impact of tropical sea surface temperature (SST) biases on the Subseasonal to Seasonal Prediction project (S2S) precipitation forecast skill over the contiguous United States (CONUS) in the Unified Forecast System (UFS) coupled model Prototype 6. Boreal summer (June–September) and winter (December–March) for 2011–18 were analyzed. The impact of tropical west Pacific (WP) and tropical North Atlantic (TNA) warm SST biases is evaluated using multivariate linear regression analysis. A warm SST bias over the WP influences the CONUS precipitation remotely through a Rossby wave train in both seasons. During boreal winter, a warm SST bias over the TNA partly affects the magnitude of the North Atlantic subtropical high (NASH)’s center, which in the reforecasts is weaker than in reanalysis. The weaker NASH favors an enhanced moisture transport from the Gulf of Mexico, leading to increased precipitation over the Southeast United States. Compared to reanalysis, during boreal summer, the NASH’s center is also weaker and in addition, its position is displaced to the northeast. The displacement further affects the CONUS summer precipitation. The SST biases over the two tropical regions and their impacts become stronger as the forecast lead increases from week 1 to 4. These tropical biases explain up to 10% of the CONUS precipitation biases on the S2S time scale.
Understanding the Digital Markets Act
Authors: Bostoen Friso
Published: April 2023

In September 2022, the European Union (EU) legislature adopted the Digital Markets Act (DMA)—a landmark piece of regulation with the potential to transform the digital economy in Europe and beyond. Even after adoption, however, questions remain about its stated goals, underlying assumptions, scope, obligations, and eventual effectiveness. This article examines these questions using EU competition law not as a touchstone but as a reference point. First, the DMA’s goals of “fairness” and “contestability” can be more accurately restated as the protection of intra-platform and the promotion of inter-platform competition. Second, the DMA is based on the idea that the enforcement of the abuse of dominance provision, Article 102 Treaty on the Functioning of the European Union (TFEU), is ineffective both procedurally (due to lengthy investigations and remedial issues) and substantively (due to the difficulty of establishing dominance and abuse)—two assumptions that must be tested by examining competition law’s track record. Third, the scope of the DMA is built around the concept of “gatekeepers,” which are in turn defined based on turnover, market capitalization, and active users. Is this an application of the resurgent “big is bad” ideology or a proxy for market power? Fourth, the DMA imposes a list of dos and don’ts on gatekeepers, many of which are inspired by past or ongoing antitrust investigations. Does this experience justify the far-reaching obligations and if so, are they sufficiently flexible to allow for procompetitive gatekeeper conduct? Finally, the DMA is based on the idea that large online platforms have not continued to deliver the desired innovation outcomes and have reaped more than their fair share of the rewards from the innovation they brought. This assumption is tested by a historical look at Apple’s App Store—the most important innovation platform to arise in the digital economy.
A Retrospective Study of the Patient State Index During General Anesthesia in Infants and Young Children
Authors: Gao Zhengzheng , Zhang Jianmin , Zhang Xuemei , Wang Liya , Huang Yao , Yu Jie
Published: April 2023

This study described electroencephalogram (EEG) parameters in children under general anesthesia, which could monitor patient-specific brain responses to anesthetics and assess the effects of anesthesia. The objective was to detect the patient state index (PSI) and associated factors. We analyzed EEG parameters in patients in the age range 1 to 36 months. Patients were stratified into 2 groups as those aged 1 to 12 months and 13 to 36 months. Sixty-two patients were involved. Spectral edge frequency (SEF), PSI, and blood pressure were lower, and burst suppression rate (BSR) and heart rate were higher in the 1 to 12 months group. The SEF was associated with PSI in both groups. Age and blood pressure were positively associated with PSI, and BSR was negatively related to PSI in children under 1 year of age. Blood pressure was not associated with PSI in the 13 to 36 months age group. We found that the PSI levels did not accurately assess the depth of anesthesia in children under 1 year of age.