bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure 5 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

NUC-7738 and 3′-dA affect the NF-κB pathway. A, Enrichment plots for NF-κB pathway for all 4 conditions. ES, Enrichment score. B, Expression levels of genes found in the leading edge of NF-κB pathway enrichment. Blue indicates downregulation and brown indicates upregulation of transcript. Significance plot indicates whether the gene was significantly differentially expressed. Red stands for Padj > 0.05 and green Padj < 0.05. Order of columns corresponds with expression heatmap. C, NF-κB activity was measured using the SEAP reporter gene assay in THP-1 cells. NF-κB activity was induced with lipopolysaccharide (LPS) in the presence or absence of NUC-7738. SEAP production as result of NF-κB activity was measured using the QuantiBlue colorimetric enzyme assay. Values were normalized to untreated LPS stimulated cells. D, NF-κB activity was induced with LPS in the presence or absence of NUC-7738 in NF-κB THP1 reporter cell line. Cells were harvested and fractionated into nuclear and cytosolic fraction. Western blot analysis using specific antibodies was employed to detect NF-κB p65 (RELA), nuclear marker Lamin B1, and cytosolic marker GAPDH. E, NF-κB p65 and Caspase 3 in ex vivo tissue treated with NUC-7738 for 24 hours. NF-κB p65 was seen in the nucleus of controls but disappeared after treatment with NUC-7738, and an increase in Caspase 3 was observed after 24 hours. H&E, Hematoxylin and eosin.
Figure 1 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

NUC-7738, ProTide version 3′-dA, has cytotoxic activity. A, Scheme of the chemical synthesis of 3′-deoxyadenosine 5′-O-phenyl-(benzyloxy-L-alaninyl)-phosphate (NUC-7738), a functionalized ProTide of 3′-dA. B, HAP1 cells were treated with different concentrations of 3′-dA or NUC-7738 and cell viability was measured after 48 hours. One representative plot is shown. C, IC50 and IC90 determination of 3′-dA or NUC-7738 was performed using a nonlinear regression model. Mean and SEM of 4 biological replicates are shown. D, Determination of IC50 of 3′-dA or NUC-7738 in gastric, renal, melanoma, and ovarian cancer cell lines. Mean and SEM of at least 3 biological replicates is shown (where no SEM is shown, only 2 biological replicates were performed). E, Gastric or cervical cancer cells were treated with NUC-7738 or 3′-dA for 24 hours, following which cleaved PARP was detected by Western blot. GAPDH was used as a loading control. F, Tera-1 cells were treated with NUC-7738 or 3′-dA for 24 hours. Early and late apoptotic and dead cells were sorted and counted after staining with Guava Nexin kit. G, Chemical perturbation of known enzymes involved in processing of 3′-dA. HAP1 cells were treated with NUC-7738 and 3′-dA in the presence or absence of the ADA antagonist EHNA, the hENT1 antagonist NBTI, or the ADK inhibitor A134974. The fold-change difference in IC50 values compared with control is shown as means with SEM (n > 3).
Supplementary Table 3 from Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma
Authors: Zhai Lijie , Bell April , Ladomersky Erik , Lauing Kristen L. , Bollu Lakshmi , Nguyen Brenda , Genet Matthew , Kim Miri , Chen Peiwen , Mi Xinlei , Wu Jennifer D. , Schipma Matthew J. , Wray Brian , Griffiths John , Unwin Richard D. , Clark Simon J. , Acharya Rajesh , Bao Riyue , Horbinski Craig , Lukas Rimas V. , Schiltz Gary E. , Wainwright Derek A.
Published: November 2024

Supplementary Table 3. Differentially expressed genes that possess the strongest correlation with IDO in human GBM cells.
Supplementary Figure 1 from Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma
Authors: Zhai Lijie , Bell April , Ladomersky Erik , Lauing Kristen L. , Bollu Lakshmi , Nguyen Brenda , Genet Matthew , Kim Miri , Chen Peiwen , Mi Xinlei , Wu Jennifer D. , Schipma Matthew J. , Wray Brian , Griffiths John , Unwin Richard D. , Clark Simon J. , Acharya Rajesh , Bao Riyue , Horbinski Craig , Lukas Rimas V. , Schiltz Gary E. , Wainwright Derek A.
Published: November 2024

Supplemental Figure 1. Overall survival of syngeneic mice with intracranial IDO-/-tGBM tumors and depleted for CD4+ T, CD8+ T, and NK1.1+ immune cells.
Supplementary fig 3 from Ovarian Cancer–Specific BRCA-like Copy-Number Aberration Classifiers Detect Mutations Associated with Homologous Recombination Deficiency in the AGO-TR1 Trial
Authors: Schouten Philip C. , Richters Lisa , Vis Daniel J. , Kommoss Stefan , van Dijk Ewald , Ernst Corinna , Kluin Roelof J.C. , Marmé Frederik , Lips Esther H. , Schmidt Sandra , Scheerman Esther , Prieske Katharina , van Deurzen Carolien H.M. , Burges Alexander , Ewing-Graham Patricia C. , Dietrich Dimo , Jager Agnes , de Gregorio Nikolaus , Hauke Jan , du Bois Andreas , Nederlof Petra M. , Wessels Lodewyk F. , Hahnen Eric , Harter Philipp , Linn Sabine C. , Schmutzler Rita K.
Published: November 2024

Supplemental Figure 3. Distance to the BRCA1 centroid. Distance to the BRCA1 mutated centroid is subtracted from the distance to the control centroid.
Supplementary Table 1 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Supplementary Table 1
Figure S5 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Figure S5
Figure S3 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Figure S3
Supplementary Data from Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer
Authors: Peng Hui , James C. Alston , Cullinan Darren R. , Hogg Graham D. , Mudd Jacqueline L. , Zuo Chong , Takchi Rony , Caldwell Katharine E. , Liu Jingxia , DeNardo David G. , Fields Ryan C. , Gillanders William E. , Goedegebuure S. Peter , Hawkins William G.
Published: November 2024

Supplementary tables and figures
Supplementary Legend from First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
Authors: Yap Timothy A. , Vieito Maria , Baldini Capucine , Sepúlveda-Sánchez Juan Manuel , Kondo Shunsuke , Simonelli Matteo , Cosman Rasha , van der Westhuizen Andre , Atkinson Victoria , Carpentier Antoine F. , Löhr Mario , Redman Rebecca , Mason Warren , Cervantes Andres , Le Rhun Emilie , Ochsenreither Sebastian , Warren Louise , Zhao Yumin , Callies Sophie , Estrem Shawn T. , Man Michael , Gandhi Leena , Avsar Emin , Melisi Davide
Published: November 2024

Supplementary Legend
Supplementary Figure S2 from First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
Authors: Yap Timothy A. , Vieito Maria , Baldini Capucine , Sepúlveda-Sánchez Juan Manuel , Kondo Shunsuke , Simonelli Matteo , Cosman Rasha , van der Westhuizen Andre , Atkinson Victoria , Carpentier Antoine F. , Löhr Mario , Redman Rebecca , Mason Warren , Cervantes Andres , Le Rhun Emilie , Ochsenreither Sebastian , Warren Louise , Zhao Yumin , Callies Sophie , Estrem Shawn T. , Man Michael , Gandhi Leena , Avsar Emin , Melisi Davide
Published: November 2024

LY3200882 pharmacokinetics parameters
Supplementary Data from First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
Authors: Yap Timothy A. , Vieito Maria , Baldini Capucine , Sepúlveda-Sánchez Juan Manuel , Kondo Shunsuke , Simonelli Matteo , Cosman Rasha , van der Westhuizen Andre , Atkinson Victoria , Carpentier Antoine F. , Löhr Mario , Redman Rebecca , Mason Warren , Cervantes Andres , Le Rhun Emilie , Ochsenreither Sebastian , Warren Louise , Zhao Yumin , Callies Sophie , Estrem Shawn T. , Man Michael , Gandhi Leena , Avsar Emin , Melisi Davide
Published: November 2024

Line graph of langerhan skin biopsy
Supplementary Figures S1-S25 from Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy
Authors: Reinstein Zachary Z. , Zhang Yue , Ospina Oscar E. , Nichols Matt D. , Chu Victoria A. , Pulido Alvaro de Mingo , Prieto Karol , Nguyen Jonathan V. , Yin Rui , Moran Segura Carlos , Usman Ahmed , Sell Brittney , Ng Spencer , de la Iglesia Janis V. , Chandra Sunandana , Sosman Jeffrey A. , Cho Raymond J. , Cheng Jeffrey B. , Ivanova Ellie , Koralov Sergei B. , Slebos Robbert J.C. , Chung Christine H. , Khushalani Nikhil I. , Messina Jane L. , Sarnaik Amod A. , Zager Jonathan S. , Sondak Vernon K. , Vaske Charles , Kim Sungjune , Brohl Andrew S. , Mi Xinlei , Pierce Brian G. , Wang Xuefeng , Fridley Brooke L. , Tsai Kenneth Y. , Choi Jaehyuk
Published: November 2024

Supplementary Fig. S1: Patient level heatmaps by assay. Supplementary Fig. S2: Overview of modalities in database. Supplementary Fig. S3: Computational pipeline for single cell RNA-seq data processing. Supplementary Fig. S4: Quality control metrics of tissue single cell data set. Supplementary Fig. S5: Cell type clusters in single-cell PBMC dataset. Supplementary Fig. S6: Myeloid cells in Merkel cell carcinoma. Supplementary Fig. S7: Response to ICB is associated with tumor cell upregulation of an interferon-γ signature. Supplementary Fig. S8: GSEA on tumor cells controlling for proliferation. Supplementary Fig. S9: Dot plot of RNA markers in CD8 clusters (tissue). Supplementary Fig. S10: Clonotype distribution between CD8 T cell lineages. Supplementary Fig. S11: CD8 lineage characterization. Supplementary Fig. S12: Clonality and neoantigen metrics of metrics of CD8 T cells. Supplementary Fig. S13: Comparisons of cell type signatures and cell proportions separated by sample origin. Supplementary Fig. S14: Epitope screening results. Supplementary Fig. S15: Public epitopes. Supplementary Fig. S16: Expression of naïve-like markers on Vδ1 T cells. Supplementary Fig. S17: GeoMx quality control for regions of interest. Supplementary Fig. S18: GeoMx image and differential expression analysis. Supplementary Fig. S19: CosMx quality control for fields of view. Supplementary Fig. S20: CosMx degree of co-localization sensitivity test shows B cell, T cell, pDC, and DC interactions. Supplementary Fig. S21: Pre-post genes. Supplementary Fig. S22: MIXCR analysis of pre-post ICB clonal dynamics. Supplementary Fig. S23: Single cell analysis of pre-post ICB clonal dynamics. Supplementary Fig. S24: Functional convergence of CD8 and γT cells. Supplementary Fig. S25: Graphical model of immune checkpoint response in MCC.
Supplementary Movie 2 from Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition
Authors: Coats Josh T. , Li Shuyu , Tanaka Tomoyuki U. , Tauro Sudhir , Sutherland Calum , Saurin Adrian T.
Published: November 2024

Supplementary Movie 2
Sleep apnea risk, subjective cognitive decline, and cognitive performance: Findings from the Boston Latino Aging Study (BLAST)
Authors: McDowell Celina , Giudicessi Averi , Martinez Jairo Enrique , Badillo-Cabrera Alex L. , Bonillas Félix Nikole A. , Martinez Lusiana , Munera Diana , Vila-Castelar Clara , Schwab Nadine , Ramirez-Gomez Liliana , Saldana Daniel Gilberto , Gonzalez Catalan Marta , Amariglio Rebecca , Duffy Jeanne F. , Cronin-Golomb Alice , Quiroz Yakeel T.
Published: November 2024

Introduction: Obstructive sleep apnea (OSA) is associated with subjective cognitive decline (SCD) and increased risk of cognitive decline and dementia. These relations are understudied in ethnoracially diverse groups. We examined associations among self-reported OSA risk, SCD, and cognitive performance in community-dwelling older Latinos. High OSA risk was hypothesized to be associated with greater SCD and worse cognitive performance.

Methods: 112 participants (40 female) from the Boston Latino Aging Study (BLAST) were included (Mage=67.0 years [SD=8.0]; Meducation=11.0 years [SD=5.1]). Participants completed the Preclinical Alzheimer’s Cognitive Composite-5 (PACC5; z-scores), the Berlin Questionnaire (high vs. low OSA risk), and the Cognitive Function Instrument (SCD). The Mini-Mental State Examination (MMSE) indexed global cognition. Hierarchical regressions assessed associations among OSA risk, SCD, and cognitive performance while controlling for demographics. T-tests examined demographic and cognitive differences between those at high/low OSA risk.

Results: On average, participants had an MMSE score of 25.9 (SD=3.7, range 11-30; 37 participants with MMSE<26) and mild SCD (CFI; M=4.2 [3.6]). OSA risk did not predict SCD (β=.09, p=.33) or PACC5 performance (β=.01, p=.92). No differences in SCD or PACC5 performance were observed between those at low vs. high OSA risk (p’s≥.21).

Conclusion: Preliminary findings suggest that self-reported OSA risk may not signal cognitive decline risk for older Latinos. Questionnaires screening for OSA may need to be used in tandem with other assessments to identify those experiencing early cognitive decline. More work with larger sample sizes is needed; BLAST data collection is ongoing.
Concomitant Use of Proton Pump Inhibitors and CDK4/6 inhibitors in Metastatic Hormone-Positive Breast Cancer: A Real World Cohort Study
Authors: karhan Ogur , İleri Serdar , Urakçı Zuhat , Arvas Hayati , Kılıç Delyadıl Karakaş , Sezgin Yasin , Erçek Berrak Merit , Tunç Sezai
Published: November 2024

Introduction: Conflicting evidence exists regarding the concurrent use of cyclin-dependent kinase (CDK) 4/6 inhibitors and proton pump inhibitors (PPIs) in the treatment of breast cancer. This study aimed to investigate whether PPI use interferes with the efficacy of CDK4/6 inhibitors.
Methods: This retrospective, multicenter, real-world study included 205 patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Patient data were collected from January 2020 to August 2023. Patients who received either ribociclib or palbociclib, with or without a PPI, were included. Median progression-free survival (mPFS) was estimated using the Kaplan-Meier method, and factors associated with mPFS were analyzed using Cox regression.
Results: Among the patients, 100 received palbociclib and 105 received ribociclib. In the palbociclib group, 40 patients (40%) used a PPI, and 60 (60%) did not. The mPFS was 16.1 months for patients with a PPI versus 22.2 months for those without (p=0.26). In the ribociclib group, 44 patients used a PPI and 61 did not use a PPI. The median PFS was comparable between patients receiving PPIs and those not receiving PPIs. (19.3 months and 20.7 months, respectively). Poor PFS was associated with liver metastasis, brain metastasis, and high Ki-67.
Conclusion: Concomitant use of PPIs with ribociclib or palbociclib did not affect the efficacy of either CDK4/6 inhibitor. PPIs can be administered alongside these medications when clinically indicated
Efeito da educação dos pais sobre o rendimento escolar dos filhos via dependência administrativa da escola
Authors: Alencar Nataniele dos Santos , Costa Edward  Martins , Khan Ahmad Saeed , Mariano Francisca Zilania , Araujo Jair Andrade de
Published: November 2024

The study seeks to measure the indirect effect of the education of mothers and fathers on the school performance of children who attend the 5th year of elementary school in Brazilian urban areas, through themediation of the type of school they attend. The method used was the Causal Mediation Effect; data are from SAEB for the year 2017. The results show that the effect is enhanced by the type of school the children attend, whether they are private or public, especially when the father has completed higher education.
Impacto de las cláusulas de transferencia tecnológica e innovación en los acuerdos comerciales regionales
Authors: Reinoso Alan Fairlie , Portocarrero Torres Jessica Milagros , Paredes Zegarra Tania Karen
Published: November 2024

El comercio internacional es uno de los principales vehículos para la transferencia tecnológica, pues contribuye a la generación de nuevos productos con mayor valor agregado, ampliando las oportunidades de exportación y la diversificación, así como la inserción de las empresas domésticas en las cadenas globales de valor. Este artículo busca determinar el impacto que tienen las cláusulas de transferencia tecnológica establecidas en los principales acuerdos comerciales firmados por los países de América Latina y el Caribe durante los últimos 20 años sobre el nivel de exportaciones, particularmente sobre la exportación de bienes en sectores intensivos en tecnología. Posteriormente, se intenta analizar si dicho efecto varía entre los acuerdos comerciales Norte-Sur y Sur-Sur, especialmente en el caso de la Alianza del Pacífico.
Happy to Help: Welfare Effects of a Nationwide Volunteering Programme
Authors: Krekel Christian , Shreedhar Ganga , Lee Helen , Marshall Claire , Boler Alison , Smith Allison , Dolan Paul
Published: November 2024

We study the wellbeing returns from volunteering in England's National Health Service (NHS) Volunteer Responders, set up in response to Covid-19. Using linked survey and administrative data, we exploit the oversubscription of volunteers and the random allocation of tasks via an app to establish causality. Volunteers show stronger wellbeing and feelings of belongingness and connectedness to their local area. Welfare analyses suggest that the benefits of the programme substantially exceeded its costs. We are the first to study the welfare effects of a nationwide volunteering programme. Our findings show that pro-social behaviour improves personal wellbeing as well as social welfare.
Multidimensional Inequality Measurement via Optimal Transport
Authors: Fan Yanqin , Henry Marc , Pass Brendan , Rivero Jorge A.
Published: November 2024

The Lorenz curve and Gini index are standard tools for the evaluation of inequality in one dimension. However, inequality is inherently multi-dimensional. Extending the Lorenz curve and Gini index to a multidimensional context has proved controversial. This paper proposes a new multivariate extension based on multivariate rearrangements of optimal transport theory, which shares many of the desirable properties of their univariate counterparts. In particular, the corresponding multivariate inequality ordering is equivalent to preference by any social planner with inequality averse multivariate rank dependent social evaluation functional.
Should Mothers Work? How Perceptions of the Social Norm Affect Individual Attitudes Toward Work in the U.S.
Authors: Cortés Patricia , Koşar Gizem , Pan Jessica , Zafar Basit
Published: November 2024

We study how peer beliefs shape individual attitudes toward maternal labor supply using hypothetical scenarios that elicit recommendations on the labor supply choices of a mother with a young child and an information treatment embedded within geographically representative surveys of the US population. Across scenarios, we find that individuals are systematically misinformed about the extent of gender conservativeness of the people around them. Exposure to information on peer beliefs leads to a shift in recommendations, driven largely by information-based belief updating. The information treatment also increases (intended and actual) donations to a non-profit organization advocating for women in the workplace.
Constitutional Implementation of Affirmative Action Policies in India
Authors: Sönmez Tayfun , Yenmez M. Bumin
Published: November 2024

India is home to a comprehensive affirmative action program that reserves a fraction of positions at governmental institutions for various disadvantaged groups. While there is a Supreme Court-endorsed mechanism to implement these reservation policies when all positions are identical, courts have refrained from endorsing explicit mechanisms when positions are heterogeneous. This lacuna has resulted in widespread adoption of unconstitutional mechanisms, countless lawsuits, and inconsistent court rulings. By formulating mandates from the landmark Supreme Court judgment Saurav Yadav vs The State of U.P. (2020) as technical axioms, we show that the 2SMH-DA mechanism is uniquely suited to overcome these challenges.
On a small collection of linyphiid spiders from mountain Phoenix, Liaoning Province, China, with the description of a new species (Linyphiidae)
Authors: TANASEVITCH ANDREI V. , MARUSIK YURI M.
Published: November 2024

A small series of spiders collected from a low mountain Phoenix in Liaoning Province of China, contains five linyphiid species, one of which, Platyspira scissa sp. nov. (♂, ♀), is described as new. The new species is similar to P. tanasevitchi Song & Li, 2009, known from caves in Guizhou Province, China. Habitus and copulatory organs of both sexes are illustrated for the new species, as well as for “Doenitzius” pruvus Oi, 1960. The taxonomic position of the genus Doenitzius Oi, 1960 is discussed. Distribution of each species is commented on.
A new species of Atarphia (Coleoptera: Nitidulidae: Nitidulinae) from Laos
Authors: GREGSON LILY M. , POWELL GARETH S.
Published: November 2024

A new species of the genus Atarphia Reitter, 1884 is described from Phongsaly province, Laos. The new species, Atarphia mammutha sp. nov., is diagnosed from the three previously described members of the genus. An updated key to the species of Atarphia and additional distributional records are provided.
Prediction of risk for early or very early preterm births using high-resolution urinary metabolomic profiling
Authors: Zhang Yaqi , Sylvester Karl G. , Wong Ronald J. , Blumenfeld Yair J. , Hwa Kuo Yuan , Chou C. James , Thyparambil Sheeno , Liao Weili , Han Zhi , Schilling James , Jin Bo , Marić Ivana , Aghaeepour Nima , Angst Martin S. , Gaudilliere Brice , Winn Virginia D. , Shaw Gary M. , Tian Lu , Luo Ruben Y. , Darmstadt Gary L. , Cohen Harvey J. , Stevenson David K. , McElhinney Doff B. , Ling Xuefeng B.
Published: November 2024

Background

Preterm birth (PTB) is a serious health problem. PTB complications is the main cause of death in infants under five years of age worldwide. The ability to accurately predict risk for PTB during early pregnancy would allow early monitoring and interventions to provide personalized care, and hence improve outcomes for the mother and infant.

Objective

This study aims to predict the risks of early preterm (< 35 weeks of gestation) or very early preterm (≤ 26 weeks of gestation) deliveries by using high-resolution maternal urinary metabolomic profiling in early pregnancy.

Design

A retrospective cohort study was conducted by two independent preterm and term cohorts using high-density weekly urine sampling. Maternal urine was collected serially at gestational weeks 8 to 24. Global metabolomics approaches were used to profile urine samples with high-resolution mass spectrometry. The significant features associated with preterm outcomes were selected by Gini Importance. Metabolite biomarker identification was performed by liquid chromatography tandem mass spectrometry (LCMS-MS). XGBoost models were developed to predict early or very early preterm delivery risk.

Setting and participants

The urine samples included 329 samples from 30 subjects at Stanford University, CA for model development, and 156 samples from 24 subjects at the University of Alabama, Birmingham, AL for validation.

Results

12 metabolites associated with PTB were selected and identified for modelling among 7,913 metabolic features in serial-collected urine samples of pregnant women. The model to predict early PTB was developed using a set of 12 metabolites that resulted in the area under the receiver operating characteristic (AUROCs) of 0.995 (95% CI: [0.992, 0.995]) and 0.964 (95% CI: [0.937, 0.964]), and sensitivities of 100% and 97.4% during development and validation testing, respectively. Using the same metabolites, the very early PTB prediction model achieved AUROCs of 0.950 (95% CI: [0.878, 0.950]) and 0.830 (95% CI: [0.687, 0.826]), and sensitivities of 95.0% and 60.0% during development and validation, respectively.

Conclusion

Models for predicting risk of early or very early preterm deliveries were developed and tested using metabolic profiling during the 1st and 2nd trimesters of pregnancy. With patient validation studies, risk prediction models may be used to identify at-risk pregnancies prompting alterations in clinical care, and to gain biological insights of preterm birth.
Loneliness, emotional support and the mental health of young adults and their parents in New York, US during the COVID-19 pandemic: a cohort study
Authors: Akinkuowo Abosede , Cheslack-Postava Keely , Skokauskas Norbert , Hoven Christina W.
Published: November 2024

Background

The coronavirus disease (COVID-19) pandemic led to social isolation and widespread lockdown, resulting in loneliness and lack of emotional support, which have been associated with adverse mental health outcomes. This study aims to explore the relationship of loneliness and emotional support with depression and substance use among young adults and their parents during the COVID-19 pandemic.

Methods

A cohort of 1227 participants was recruited from three ongoing cohort studies in the metropolitan area of New York City, USA. Data was collected through telephone interviews using preset questionnaires during wave 1 (March-August 2020), wave 2 (September 2020-February 2021) and wave 3 (March-August 2021) of the COVID-19 pandemic. Logistic regression models were used to test the association between loneliness and emotional support, and the mental health outcomes; depression and substance use, with adjustments made for age, gender, race, employment status, living conditions, and marital status. Additionally, the effect modification of respondent type and living alone or with others was examined.

Results

At wave 1, loneliness showed a significant positive association with depressive symptoms (OR: 2.56, 95%CI: 2.19-3.00, P = < 0.001) and an increase in substance use, such as smoking tobacco using cigarettes, pipes, or cigar (OR: 1.59, 95%CI: 1.24–2.04, P = < 0.001), alcohol consumption (OR: 1.23, 95%CI: 1.07–1.42, P = 0.003), and marijuana/other substances (OR: 1.57, 95%CI: 1.26–1.96, P = < 0.001). Conversely, emotional support showed a significant negative association with depressive symptoms (OR: 0.71, 95%CI: 0.62–0.81, P = < 0.001) but a non-significant association with increase in tobacco smoking using vapes and e-cigarettes, alcohol consumption and marijuana and other substances. However, a significant negative association was observed between emotional support, and increased tobacco smoking using cigarettes, pipes, or cigar (OR: 0.73, 95%CI: 0.58–0.93, P = 0.011). The associations of loneliness and emotional support with mental health outcomes were stronger at wave 2 compared to wave 1. The modifier effects of respondent type and living condition were non-significant.

Conclusions

This study indicates that increased loneliness is associated with a higher likelihood of depression and substance use, while higher emotional support is linked to a reduced likelihood of depressive symptoms during the COVID-19 pandemic.
Trends in the use and nonmedical use of sedatives-hypnotics in the population aged 12 to 64 years in Taiwan: a comparative analysis of the national surveys in 2014 and 2018
Authors: Tsay Wei-Yi , Chen Lian-Yu , Wu Shang-Chi , Hsiao Po-Chang , Ting Te-Tien , Yen Cheng-Fang , Chang Shu-Sen , Li Chung-Yi , Yang Hao-Jan , Yen Chia-Feng , Chen Chuan-Yu , Huang Jiun-Hau , Tu Yu-Kang , Chen Wei J.
Published: November 2024

Background

Many countries, including Taiwan, have tightened regulations on prescribing sedatives-hypnotics over the concern of their associated adverse health effects. However, it remains seldom investigated whether different age-sex strata have differential trends in national surveys over time for either the use or nonmedical use (NMU) of sedatives-hypnotics. Comparing Taiwan’s two national surveys in 2014 and 2018, we aimed to examine (1) the population’s trends for the prevalence of past-year use and NMU of sedatives-hypnotics overall and in age-sex strata; (2) trends for sociodemographic subgroups for those age-sex strata with significant changes in past-year use and NMU of sedatives-hypnotics over time; and (3) trends for sources of and motives for NMU of sedatives-hypnotics.

Methods

The national survey enrolled 17,837 participants in 2014 (response rate = 62.2%) and 18,626 participants in 2018 (response rate = 64.6%) of citizens aged 12–64 years. Each participant anonymously completed a computer-assisted self-interview. The questionnaire consisted of sociodemographic variables and the use of various psychoactive substances and sedative-hypnotics, among others. NMU of sedative-hypnotics was defined as using the drug without a prescription, or more frequently, or in larger doses than prescribed. To compare the prevalence between the two waves, we conducted multivariable logistic regression analysis and the difference-in-differences in prevalence was examined with an interaction term between survey year and sex.

Results

We found decreasing trends in young adult (18–39 years old) males for both past-year use (3.07–2.29%) and NMU (0.84–0.18%), but increasing trends in adolescents (0.42–0.80%) and young adult females (2.91–3.81%) for past-year use and in adolescents (0.16–0.39%) and middle-aged adult (40–64 years old) females (0.73–1.14%) for past-year NMU of sedatives-hypnotics. Among the young and middle-aged adult females, the increasing trends for past-year use and NMU, respectively, were found to occur mainly in certain sociodemographic subgroups, with alcohol users being the overlapping subgroup.

Conclusions

The differential trends over time of past-year use or NMU of sedatives-hypnotics in different age-sex strata in the population have policy implications to curtail the increasing trend over time.
A machine learning-based approach for constructing a 3D apparent geological model using multi-resistivity data
Authors: Puntu Jordi Mahardika , Chang Ping-Yu , Amania Haiyina Hasbia , Lin Ding-Jiun , Suryantara M. Syahdan Akbar , Tsai Jui-Pin , Yu Hwa-Lung , Chang Liang-Cheng , Zeng Jun-Ru , Kassie Lingerew Nebere
Published: November 2024

This study presents a comprehensive approach for constructing a 3D Apparent Geological Model (AGM) by integrating multi-resistivity data using statistical methods, supervised machine learning (SML), and Python-based modeling techniques. Demonstrated through a case study in the Choushui River Alluvial Fan (CRAF) in Taiwan, the methodology enhances data coverage significantly, from 62 to 386 points, by incorporating resistivity data sets from Vertical Electrical Sounding (VES), Transient Electromagnetic (TEM), and borehole information. A key contribution of this work is the rigorous harmonization of these data sets, ensuring consistent resistivity values across different methods before constructing the 3D resistivity model, addressing a gap in previous studies that typically handled these data sets separately, either building models individually or comparing results side-by-side without fully integrating the data. Furthermore, python-based modeling and radial basis function interpolation were employed to construct the 3D resistivity model for greater flexibility and effectiveness than conventional software. Subsequently, this model was transformed into a 3D AGM using the SML technique. Four algorithms, namely, random forest (RF), decision tree (DT), support vector machine (SVM), and extreme gradient boosting (XGBoost) were implemented. Following evaluation via confusion matrix analysis, evaluation metrics, and examination of receiver operating characteristics curve, it emerged that the RF algorithm exhibits superior performance when applied to our multi-resistivity data set. The results from the 3D AGM unveil distinct resistivity anomalies correlated with sediment types. The clay layer exhibited low resistivity (≤ 59.98 Ωm), while the sand layer displayed medium resistivity (59.98 < ρ < 136.14 Ωm), and the gravel layer is characterized by high resistivity ( ≥ 136.14 Ωm). Notably, in the proximal fan, gravel layers predominate, whereas the middle fan primarily consists of sandy clay layers. Conversely, the distal fan, located in the western coastal area, predominantly comprises clayey sand. To conclude, the findings of this study provide valuable insights for researchers to construct the 3D AGM from the resistivity data, applicable not only to the CRAF but also to other target areas.
Stress-induced premature senescence in high five cell cultures: a principal factor in cell-density effects
Authors: Min Rui , Zhang Dahe , He Mingzhe , Chen Jingyuan , Yi Xiaoping , Zhuang Yingping
Published: November 2024

The Baculovirus Expression Vector System (BEVS) is highly valued in vaccine development, protein engineering, and drug metabolism research due to its biosafety, operational convenience, rapid scalability, and capacity for self-assembling virus-like particles. However, increasing cell density at the time of inoculation severely compromises the production capacity of BEVS, resulting in the “cell density effect”. This study aimed to explore the mechanisms of the cell density effect through time-series analysis of transcriptomes and proteomes, with the goal of overcoming or alleviating the decline in productivity caused by increased cell density. The dynamic analysis of the omics of High Five cells under different CCI (cell density at infection) conditions showed that the impact of the “cell density effect” increased over time, particularly affecting genetic information processing, error repair, protein expression regulation, and material energy metabolism. Omics analysis of the growth stage of High Five cells showed that after 36 h of culture (cell density of about 1 × 106 cells/mL), the expression of ribosome-related proteins decreased, resulting in a rapid decrease in protein synthesis capacity, which was a key indicator of cell aging. Senescence verification experiments showed that cells began to show obvious early aging characteristics after 36 h, resulting in a decrease in the host cell’s ability to resist stress. Overexpression and siRNA inhibition studies showed that the ndufa12 gene was a potential regulatory target for restricting the “cell density effect”. Our results suggested that stress-induced premature senescence in High Five cell cultures, resulting in reduced energy metabolism and protein synthesis capabilities, was a critical factor contributing to cell density effects, and ultimately affecting virus production. In conclusion, this study provided new insights into managing virus production limitations due to cell density effects and offered innovative strategies to mitigate the adverse effects of cellular aging in biomanufacturing technologies.

Graphical abstract
Co-reactivity pattern of glucose metabolism and blood perfusion revealing DNA mismatch repair deficiency based on PET/DCE-MRI in endometrial cancer
Authors: Li Xiaoran , Cui Bixiao , Wang Shijun , Gao Min , Xing Qiuyun , Liu Huawei , Lu Jie
Published: November 2024

Background

Identifying DNA mismatch repair deficiency (MMRd) is important for prognosis risk stratification in patients with early-stage endometrial cancer (EC), but there is a notable absence of cost-effective and non-invasive preoperative assessment techniques. The study explored the co-reactivity pattern of glucose metabolism and blood perfusion in EC based on hybrid [18F]fluorodeoxyglucose ([18F]FDG) PET/dynamic contrast enhanced (DCE)-MRI to provide an imaging biomarker for identifying MMRd.

Methods

Patients with a history of postmenopausal bleeding and initially diagnosed with EC on ultrasound were recruited to perform a PET/DCE-MRI scan. Glucose metabolism parameters were calculated on PET, and blood perfusion parameters were calculated semi-automatically by the DCE-Tofts pharmacokinetic model. The MMRd of early-stage EC was evaluated by immunohistochemistry. The synchronous variation of PET and DCE-MRI parameters was compared between the MMRd and mismatch repair proficiency (MMRp). The association between PET/DCE-MRI and MMRd was analyzed by logistic regression to establish the digital biomarker for predicting MMRd. Receiver operating characteristic curve, decision curve analysis, and the net reclassification index (NRI) were used to evaluate the value of the digital biomarker in identifying MMRd.

Results

Eighty-six early-stage EC cases (58.92 ± 10.13 years old, 34 MMRd) were enrolled. The max/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume, total lesion glycolysis, transfer constant (Ktrans), and efflux rate (Kep) were higher in MMRd than those in MMRp (P < 0.001, < 0.001, 0.002, 0.004, < 0.001, and 0.005, respectively). The correlations between glucose metabolism and blood perfusion were different between the MMRd and MMRp subgroups. SUVmax was correlated with Kep (r = 0.36) in the MMRd. SUVmean (odds ratio [OR] = 1.32, P = 0.006) and Ktrans (OR = 1.90, P = 0.021) were independent risk factors for MMRd. And the digital biomarker that combined SUVmean and Ktrans outperformed in identifying MMRd in early-stage EC more than DCE-MRI (AUC: 0.83 vs. 0.78, NRI = 13%).

Conclusion

A potential digital biomarker based on [18F]FDG PET/DCE-MRI can identify MMRd for prognosis risk stratification in early-stage EC.
Discovery of novel CDK2 inhibitors for cancer treatment: integrating ligand-based pharmacophore modelling, molecular docking, DFT, ADMET, and molecular dynamics simulation studies
Authors: Chagaleti Bharath Kumar , Saravanan Venkatesan , Kathiravan M. K.
Published: November 2024

Background

The global landscape of public health faces significant challenges attributed to the prevalence of cancer and the emergence of treatment resistance. This study addresses these challenges by focusing on Cyclin-dependent Kinase 2 (CDK2) and employing a systematic computational approach for the discovery of novel cancer therapeutics.

Results

Initial ligand-based pharmacophore modelling, utilizing a training set of five reported CDK2 inhibitors, yielded a robust model characterized by Aro|Hyd| and |Acc|Don| features. Screening this validated model against the ZINC database identified 1881 hits, which were further subjected to molecular docking studies. The top 10 compounds (Z1–Z10) selected from the docking studies underwent Pharmacokinetic parameters Absorption, Distribution, Metabolism, Excretion and Toxicity profiling, Density Functional Theory (DFT) studies and the top two went for 100ns molecular dynamics (MD) simulations by comparing them with the standard Roscovitine. Compounds Z1 and Z2 emerged as the most promising, with docking scores of − 8.05 kcal/mol and − 8.02 kcal/mol, respectively. DFT analysis of the top 10 compounds revealed minimal variations in highest occupied molecular orbital–lowest unoccupied molecular orbital energy gaps, indicating consistent electronic stability and reactivity across the candidates. MD simulations of Z1 and Z2 confirmed their stable interactions with CDK2, with root mean square deviation (RMSD) values ranging from 1.4 to 2.5 Å for Z1 and 1.5 to 2.4 Å for Z2.

Conclusion

The current research identified compounds Z1 and Z2, which demonstrated significant potential as potent CDK2 inhibitors for cancer therapy, providing valuable insights into the development of more effective CDK2 inhibitors and addressing the critical need for innovative therapeutic strategies in cancer treatment.

Graphical abstract
Gwendolyn Brooks: Who Ya Talkin’ With?
Authors: Foster Tonya M.
Published: November 2024

This essay looks at the shifting poetic and aesthetic strategies that Gwendolyn Brooks employed over her more than fifty-year career. The first Black American poet to receive a Pulitzer Prize for Poetry, Brooks initiates a lineage of poetry and poets dedicated to attending to the daily conditions of Black life in America. Long a poet of daily Black life, Brooks announces via her poetry an aesthetics committed to, in the words of Langston Hughes, “the inherent expressions of Negro life in America: the eternal tom-tom beating in the Negro soul — the tom-tom of revolt against weariness in a white world, a world of subway trains, and work, work, work; the tom-tom of joy and laughter, and pain swallowed in a smile.” Through textual analyses of the language of several of Brooks's poems alongside interviews with Brooks and critical essays about Brooks's work, this essay points to Brooks as the poet most steadfastly exploring what philosopher George Yancy describes as “the lived density of race.” Yancy notes that “while the focus on demonstrating the nonreferential status of race is important work within the context of liberation praxis vis-a-vis racism — indeed indispensable work —  . . . it is at the level of the lived density of race that so much more work needs to be done.” This is the work of Gwendolyn Brooks's art.
Order and Archive: A Foucault Abecedary
Authors: Huffer Lynne
Published: November 2024

This essay reviews the first and last volumes of Stuart Elden's four-volume intellectual biography of Michel Foucault, The Early Foucault (2021) and Foucault's Last Decade (2016). It borrows from Roland Barthes an abecedarian method to experiment with the play between order and archive that subtends Elden's Foucault series. Like Foucault, Elden deploys an explicitly archival method for thinking philosophically. That method brings both historiographical and conceptual clarity to our understanding of Foucault within the chronological frame of his life. As a poetic order, the acrostic experimentation of abecedarian writing brings into view the nonchronological archival murmur that both shapes and exceeds Elden's ordering of fragments in dossiers and the gaps between them.
Writer and Thinker
Authors: Eiland Howard
Published: November 2024

In The Benjamin Files (2020), Fredric Jameson showcases Benjamin the writer. Adapting Roland Barthes's term “writerly” (scriptible), he emphasizes the panoramic variety of Benjamin's production together with its experimental character, its deployment of montage techniques akin to those of filmmakers and poets of his day. Jameson shows how the polyphony and multiperspectivity of Benjaminian forms reflect a monadological theory of history as “periodization without transitions.” Pablo Oyarzun's Doing Justice: Three Essays on Walter Benjamin (translated by Stephen Gingerich, 2020), views Benjamin in the context of a philosophic eventism and an ontological theory of language as revelation. Underscoring the centrality of the concepts of experience and translation in Benjamin's thinking, and providing relevant personal testimony concerning recent Chilean history, Oyarzun presents Benjamin as the “thinker of justice.” The call for justice, understood as a nonlegalistic promissory directive, entails a philosophical-historical stewardship: doing justice means worldly attentiveness to the particularity of things.
To Be Free! The Art of Gavin Jantjes
Authors: Hassan Salah M.
Published: November 2024

This article contemplates the life and work of the Oxford-based South African artist and activist Gavin Jantjes, born in 1948 when apartheid officially became the law of the land in South Africa with the National Party’s election to power. Because Jantjes’s understanding of his role as an artist took shape in Cape Town in the 1960s, when every aspect of his life was dominated by the racism of the apartheid state, he has questioned both the incongruities of his life and what his role as an artist has meant, establishing himself as an outspoken and imaginative critic of institutionalized racism and other forms of discrimination. Facing the dual obstacles of race and poverty, as well as the pejorative assumption of the Western European modernist canon that Africans lacked the ability to produce meaningful contemporary visual art, Jantjes engaged head on as an artist and activist with tensions between Western modernism and classical African art and the trope of “primitivism” in Eurocentric art historical discourses. This article foregrounds Jantjes’s multiple roles, both in and outside of the studio and gallery spaces, by examining his paintings, prints, and drawings, as well as material related to his curatorial interventions, writings, and formidable publishing efforts, to reveal pivotal moments in his personal and artistic journeys across five distinct yet overlapping phases of his artistic movement from 1970 to 2023.
The Paintings of Henok Melkamzer
Authors: Giorgis Elizabeth W.
Published: November 2024

The formal properties, styles, and techniques of telsem fascinates viewers from Ethiopia and abroad. Drawn traditionally on parchment and in acrylic in contemporary times, the sophisticated and intricate lines of telsem consist of symbols that are spectacularly expressive. However, the conventional knowledge base for telsem art in Western art-historical provisions has been cabalistic. Modernism, as a field of study, persists in classifying the sophisticated forms, exuberant colors, lines, shapes, and conceptually complex arrangement of telsem paintings in categories that are outside of the modernist canon. While Western art critics acknowledge the exquisite imagery of telsem art, they place emphasis on the disciplinary divide and difference between the visual languages of European art forms, which are modern and historical, and non-Western art forms such as telsem, which are perceived as ahistorical objects. Even though they are practiced in contemporary times, they are still approached in anthropological designations. Certainly, the uses of the supernatural in non-Western visual art are grouped together under the rubric of magical realism, and humanistic scholars have given little significance to the substantial modernist interventions of such works. These complex works of art cannot be purely described in terms of contrasts such as reality versus fantasy or in contexts of a long-gone tradition that has waned. They are still produced in contemporary times, fantastically depicting specific cultural, political, and social experiences of the contemporary moment in both rational and mythical ways. It is precisely this underlying difference in art-historical studies that the Sharjah Art Foundation’s 2024 exhibition Henok Melkamzer: Telsem Symbols and Imagery attempts to extend.