bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applications of mixture methods in epidemiological studies investigating the health impact of persistent organic pollutants exposures: a scoping review
Authors: Pan Shudi , Li Zhenjiang , Rubbo Bruna , Quon-Chow Victoria , Chen Jiawen Carmen , Baumert Brittney O. , Garcia Erika , Aung Max T. , Conti David V. , Chatzi Lida 
Published: September 2024

Abstract
Background
Persistent organic pollutants (POPs) are environmental chemicals characterized by long half-lives in nature and human bodies, posing significant health risks. The concept of the exposome, encompassing all lifetime environmental exposures, underscores the importance of studying POP as mixtures rather than in isolation. The increasing body of evidence on the health impacts of POP mixtures necessitates the proper application of statistical methods.

Objectives
We aimed to summarize studies on the overall effects of POP mixtures, identify patterns in applications of mixture methods—statistical methods for investigating the association of mixtures—and highlight current challenges in synthesizing epidemiologic evidence of POP mixtures on health effects as illustrated through a case study.

Methods
We conducted a systematic literature search on PubMed and Embase for epidemiological studies published between January 2011 and April 2023.

Results
We included 240 studies that met our eligibility criteria. 126 studies focused on per- and polyfluoroalkyl substances (PFAS) mixtures only, while 40 analyzed three or more classes of POPs in mixture analyses. We identified 23 unique mixture methods used to estimate the overall effects of POP mixtures, with Bayesian Kernel Machine Regression (BKMR), a type of response-surface modeling, being the most common. Additionally, 22.9% of studies used a combination of methods, including response-surface modeling, index modeling, dimension reduction, and latent variable models. The most extensively explored health outcome category was body weight and birth sizes (n = 43), and neurological outcomes (n = 41). In the case study of PFAS mixtures and birth weight, 12 studies showed negative associations, while 4 showed null results, and 2 showed positive associations.

Impact Statement

This scoping review consolidates the existing literature on the overall effects of POP mixtures using statistical methods. By providing a comprehensive overview, our study illuminates the present landscape of knowledge in this field and underscores the methodological hurdles prevalent in epidemiological studies focused on POP mixtures. Through this analysis, we aim to steer future research directions, fostering a more nuanced comprehension of the intricate dynamics involved in assessing the health effects of POP mixtures. Our work stands as a significant contribution to the ongoing exploration of the chemical exposome.
Whole-brain turbulent dynamics predict responsiveness to pharmacological treatment in major depressive disorder
Authors: Escrichs Anira , Sanz Perl Yonatan , Fisher Patrick M. , Martínez-Molina Noelia , G-Guzman Elvira , Frokjaer Vibe G. , Kringelbach Morten L. , Knudsen Gitte M. , Deco Gustavo 
Published: September 2024

Abstract
Depression is a multifactorial clinical syndrome with a low pharmacological treatment response rate. Therefore, identifying predictors of treatment response capable of providing the basis for future developments of individualized therapies is crucial. Here, we applied model-free and model-based measures of whole-brain turbulent dynamics in resting-state functional magnetic resonance imaging (fMRI) in healthy controls and unmedicated depressed patients. After eight weeks of treatment with selective serotonin reuptake inhibitors (SSRIs), patients were classified as responders and non-responders according to the Hamilton Depression Rating Scale 6 (HAMD6). Using the model-free approach, we found that compared to healthy controls and responder patients, non-responder patients presented disruption of the information transmission across spacetime scales. Furthermore, our results revealed that baseline turbulence level is positively correlated with beneficial pharmacological treatment outcomes. Importantly, our model-free approach enabled prediction of which patients would turn out to be non-responders. Finally, our model-based approach provides mechanistic evidence that non-responder patients are less sensitive to stimulation and, consequently, less prone to respond to treatment. Overall, we demonstrated that different levels of turbulent dynamics are suitable for predicting response to SSRIs treatment in depression.
A spatiotemporal comparative analysis on tumor immune microenvironment characteristics between neoadjuvant chemotherapy and preoperative immunotherapy for ESCC
Authors: Zhou Zhengyang , Zhang Hongdian , Du Jian , Yang Jiayu , Pan Wen , Zhang Qiumo , Wang Huiya , Tang Peng , Ba Yi , Zhang Haiyang 
Published: September 2024

AbstractThe average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level. Here, we presented the TME characters of ESCC from the temporal and spatial dimensions using scRNA-seq and ST, investigated the changes of immune cell clusters in the TME under neoadjuvant chemotherapy and preoperative immunotherapy, and explored the potential mechanisms. It was found that compared with chemotherapy, immunotherapy combined with chemotherapy increased the level of T cell proliferation, partially restored the function of exhausted T cells, induced the expansion of specific exhausted CD8 T cells, increased the production of dendritic cells (DCs), and supported the immune hot microenvironment of the tumor. We also found that CD52 and ID3 have potential as biomarkers of ESCC. Particularly, CD52 may be served as a predictor of the efficacy to screen the advantaged population of different regimens. Through multiple pathways, CAF2 and CAF5’s antigen-presenting role affected the other fibroblast clusters, resulting in malignant transformation. We analyzed the immune microenvironment differences between the two regimens to provide a more thorough description of the ESCC microenvironment profile and serve as a foundation for customized neoadjuvant treatment of ESCC.
Fabrication of a peptide–AuNP–TiO2 nanocomposite and its application as a VOC sensor
Authors: Iwakiri Toma , Suzuki Hikari , Mastubara Shogo , Higuchi Masahiro 
Published: September 2024

AbstractWe fabricated a volatile organic compound (VOC) sensor with a peptide–Au nanoparticle (AuNP)–TiO2 nanocomposite in which AuNPs were linked with TiO2-coated conductive peptide nanowires. The conductive peptide nanowires were formed between the AuNPs via self-assembly through the complexation of amphiphilic peptides, LESEHEKLKSKHKSKLKEHESEL, and Co(II). Furthermore, TiO2 mineralization on the surface of the peptide nanowires yielded mixed crystals of rutile and anatase, which exhibited highly effective photolytic activity. In particular, the obtained TiO2 exhibited three times greater photodecomposition activity in the unsintered state toward organic matter than did commercially available TiO2. Next, we constructed a VOC sensor by immobilizing peptide–AuNP–TiO2 nanocomposites on a comb electrode. The electrochemical properties of the nanocomposite changed drastically under light irradiation in the presence of VOCs, indicating transport of the VOC-decomposition-generated photoexcited electrons of TiO2 to AuNPs through conductive peptide nanowires, which prevented electron–hole recombination. The obtained sensor exhibited a sensing range of 2–100 ppm for dichloromethane, which was used as a representative VOC. Therefore, nanocomposites made of AuNPs linked with conductive TiO2 nanotubes may be highly effective for TiO2-driven VOC decomposition. Moreover, we believe that this nanocomposite has high sensitivity for sensing VOCs.
Genomic Balancing Act: deciphering DNA rearrangements in the complex chromosomal aberration involving 5p15.2, 2q31.1, and 18q21.32
Authors: Dardas Zain , Marafi Dana , Duan Ruizhi , Fatih Jawid M. , El-Rashidy Omnia F. , Grochowski Christopher M. , Carvalho Claudia M. B. , Jhangiani Shalini N. , Bi Weimin , Du Haowei , Gibbs Richard A. , Posey Jennifer E. , Calame Daniel G. , Zaki Maha S. , Lupski James R. 
Published: September 2024

Abstract
Despite extensive research into the genetic underpinnings of neurodevelopmental disorders (NDD), many clinical cases remain unresolved. We studied a female proband with a NDD, mildly dysmorphic facial features, and brain stem hypoplasia on neuroimaging. Comprehensive genomic analyses revealed a terminal 5p loss and a terminal 18q gain in the proband while a diploid copy number for chromosomes 5 and 18 in both parents. Genomic investigations in the proband identified an unbalanced translocation t(5;18) with additional genetic material from chromosome 2 (2q31.3) inserted at the breakpoint, pointing to a complex chromosomal rearrangement (CCR) involving 5p15.2, 2q31.3, and 18q21.32. Breakpoint junction analyses enabled by long-read genome sequencing unveiled the presence of four distinct junctions in the father, who is a carrier of a balanced CCR. The proband inherited from the father both the abnormal chromosome 5 resulting in segmental aneusomies of chr5 (loss) and chr18 (gain) and a der(2) homologue. Evidences suggest a chromoplexy mechanism for this CCR derivation, involving double-strand breaks (DSBs) repaired by non-homologous end joining (NHEJ) or alternative end joining (alt-EJ). The complexity of the CCR and the segregation of homologues elucidate the genetic model for this family. This study demonstrates the importance of combining multiple genomic technologies to uncover genetic causes of complex neurodevelopmental syndromes and to better understand genetic disease mechanisms.
Targeting PRMT3 impairs methylation and oligomerization of HSP60 to boost anti-tumor immunity by activating cGAS/STING signaling
Authors: Shi Yunxing , Wu Zongfeng , Liu Shaoru , Zuo Dinglan , Niu Yi , Qiu Yuxiong , Qiao Liang , He Wei , Qiu Jiliang , Yuan Yunfei , Wang Guocan , Li Binkui 
Published: September 2024

AbstractImmune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), but resistance to ICB occurs and patient responses vary. Here, we uncover protein arginine methyltransferase 3 (PRMT3) as a driver for immunotherapy resistance in HCC. We show that PRMT3 expression is induced by ICB-activated T cells via an interferon-gamma (IFNγ)-STAT1 signaling pathway, and higher PRMT3 expression levels correlate with reduced numbers of tumor-infiltrating CD8+ T cells and poorer response to ICB. Genetic depletion or pharmacological inhibition of PRMT3 elicits an influx of T cells into tumors and reduces tumor size in HCC mouse models. Mechanistically, PRMT3 methylates HSP60 at R446 to induce HSP60 oligomerization and maintain mitochondrial homeostasis. Targeting PRMT3-dependent HSP60 methylation disrupts mitochondrial integrity and increases mitochondrial DNA (mtDNA) leakage, which results in cGAS/STING-mediated anti-tumor immunity. Lastly, blocking PRMT3 functions synergize with PD-1 blockade in HCC mouse models. Our study thus identifies PRMT3 as a potential biomarker and therapeutic target to overcome immunotherapy resistance in HCC.
WHO International Standards for antibodies to HPV6 HPV11 HPV31 HPV33 HPV45 HPV52 and HPV58
Authors: Kemp Troy J. , Panicker Gitika , Eklund Carina , Nie Jianhui , Wang Youchun , Beddows Simon , Rigsby Peter , Huang Weijin , Dillner Joakim , Unger Elizabeth R. , Pinto Ligia A. , Wilkinson Dianna E. ,   the collaborative study participants, Licciardi Paul , Toh Zheng Quan , Müller Martin , Rajanathan T. M. Chozhavel , Li Shaowei , Xia Ningshao , Liu Ge , Zhou Chenliang , Zhou Lingyun , Xu Nan , Panwar Kavita , Galloway Denise , Carter Jody 
Published: September 2024

AbstractPreviously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays.
CD71 expressing circulating neutrophils serve as a novel prognostic biomarker for metastatic spread and reduced outcome in pancreatic ductal adenocarcinoma patients
Authors: Hansen Frederik J. , Mittelstädt Anke , Clausen Finn-Niklas , Knoedler Samuel , Knoedler Leonard , Klöckner Sebastian , Kuchenreuther Isabelle , Mazurie Johanne , Arnold Lisa-Sophie , Anthuber Anna , Jacobsen Anne , Merkel Susanne , Weisel Nadine , Klösch Bettina , Karabiber Alara , Tacyildiz Irem , Czubayko Franziska , Reitberger Helena , Gendy Amr El , Brunner Maximilian , Krautz Christian , Wolff Kerstin , Mihai Sidonia , Neufert Clemens , Siebler Jürgen , Grützmann Robert , Weber Georg F. , David Paul 
Published: September 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, presenting a persisting global health burden. Neutrophils have a double-edged role in tumor progression exhibiting both pro-tumor and anti-tumor functions. CD71, also known as transferrin receptor 1, performs a critical role in cellular iron uptake and is highly expressed on proliferating cells, and especially on activated immune cells. CD71 is known to be elevated in various types of solid cancers and is associated with poor prognosis, however, the expression of CD71 on neutrophils in PDAC and its potential clinical impact is still unknown. Therefore, we analyzed CD71 on circulating neutrophils in PDAC and clinical control patients and found a significant increased expression in PDAC patients. High expression of CD71 on neutrophils in PDAC patients was associated with reduced outcome compared to low expression. CD71 on neutrophils correlated positively with the levels of proinflammatory cytokines IL-6, IFN-γ, and growth factor ligands CD40-L, and BAFF in plasma of PDAC patients. Finally, we have demonstrated that high expression of CD71 on neutrophils was also associated with an increased expression of CD39 and CD25 on circulating T-cells. Based on our findings, we hypothesize that CD71 on neutrophils is associated with tumor progression in PDAC. Further studies are required to investigate the distinct functionality of CD71 expressing neutrophils and their potential clinical application.
Study concerning the design and functionality of individual emergency shelters
Authors: Ene Mircea Costin , Simion Ionel , Valter Matei 
Published: September 2024

AbstractThe divide between the rich and poor in the European housing market is fast rising. Latest research indicates that Europe is dealing with an increasing number of homeless people. Every city in Europe has them—homeless people compelled to live on street corners, frequently hiding themselves with cardboard. Rain, snow, and temperatures below zero pose a threat to their lives on a daily basis. There are many varied kinds of services that have been discovered, but it is difficult to keep track of everyone and guarantee that they have a warm night's sleep in the winter. The current article suggests accommodation as a workaround until they can receive high-intensity support, a way to keep a single person warm and safe during the winter. The focus is on devising a strategy that not only ensures the warmth and safety of individuals during the harsh winter months but also seeks to industrialize the construction of shelters, ensuring affordability below the cost of winter hospitalization for a homeless person. Crucially, the article introduces an additional layer to this initiative by highlighting the dual purpose of these individual shelters. Beyond being a means to provide respite for the homeless during severe weather, these shelters are envisioned as immediate response units in the event of emergencies such as earthquakes in urban areas. The article explores the potential impact of this multi-layered approach on transforming urban landscapes and fostering resilient communities.
On the effects of impulsivity and compulsivity on neural correlates of model-based performance
Authors: Dück Kerstin , Wüllhorst Raoul , Overmeyer Rebecca , Endrass Tanja 
Published: September 2024

AbstractImpaired goal-directed behavior is associated with a range of mental disorders, implicating underlying transdiagnostic factors. While compulsivity has been linked to reduced model-based (MB) control, impulsivity has rarely been studied in the context of reinforcement learning despite its links to reward processing and cognitive control. This study investigated the neural mechanisms underlying MB control and the influence of impulsivity and compulsivity, using EEG data from 238 individuals during a two-step decision making task. Single-trial analyses revealed a modulation of the feedback-related negativity (FRN), where amplitudes were higher after common transitions and positive reward prediction error (RPE), indicating a valence effect. Meanwhile, enhanced P3 amplitudes after rare transitions and both positive and negative RPE possibly reflect surprise. In a second step, we regressed the mean b values of the effect of RPE on the EEG signals onto self-reported impulsivity and compulsivity and behavioral MB control (w). The effect of RPE on FRN-related activity was mainly associated with higher w scores, linking the FRN to MB control. Crucially, the modulation of the P3 by RPE was negatively associated with compulsivity, pointing to a deficient mental model in highly compulsive individuals.
Nanophotonic structure inverse design for switching application using deep learning
Authors: Adibnia Ehsan , Ghadrdan Majid , Mansouri-Birjandi Mohammad Ali 
Published: September 2024

AbstractSwitching functionality is pivotal in advancing communication systems, serving as a paramount mechanism. Despite numerous innovations in this field, optical switch design, fabrication, and characterization have traditionally followed an iterative approach. Within this paradigm, the designer formulates an informed conjecture regarding the switch's structural configuration and subsequently resolves Maxwell's equations to ascertain its performance. Conversely, the inverse problem, which entails deriving a switch geometry to achieve a targeted electromagnetic response, continues to pose formidable challenges and necessitates substantial time and effort, particularly under the constraints of specific assumptions. In this work, we propose a deep neural network-based method to approximate the spectral transmittance of all-optical switches. The findings substantiate the efficacy of deep learning in the design of all-optical plasmonic switches, which are renowned as the fastest switches at the nanoscale. The nonlinear Kerr effect in square resonators is leveraged to demonstrate the switching performance. Juxtaposed with conventional simulations, the proposed model showcases a remarkable improvement in computational efficiency. Furthermore, deep learning can resolve nanophotonic inverse design problems without reliance on trial-and-error or empirical strategies. Compared to simulations, the mean squared error for both forward and inverse models is meager, with values of around 0.03 and 0.02, respectively. The deep learning-proposed switches exhibit excellent suitability for integration into photonic integrated circuits, substantially influencing the progression of all-optical signal processing.
Robust future intensification of winter precipitation over the United States
Authors: Akinsanola Akintomide A. , Chen Ziming , Kooperman Gabriel J. , Bobde Vishal 
Published: September 2024

AbstractWe investigate 21st-century hydroclimate changes over the United States (US) during winter and the sources of projection uncertainty under three emission scenarios (SSP2–4.5, SSP3–7.0, and SSP5–8.5) using CMIP6 models. Our study reveals a robust intensification of winter precipitation across the US, except in the Southern Great Plains, where changes are very small. By the end of the 21st century, winter precipitation is projected to increase by about 2–5% K−1 over most of the US. The frequency of very wet winters is also expected to increase, with 6–7 out of 30 winters exceeding the very wet threshold under the different scenarios. Our results suggest that the enhancement of future winter precipitation is modulated largely by coupled dynamic and thermodynamic responses, though partly offset by thermodynamic responses. Overall, our results highlight a high likelihood of increasing impacts from winter precipitation due to climate change.
The fitness cost of spurious phosphorylation
Authors: Bradley David , Hogrebe Alexander , Dandage Rohan , Dubé Alexandre K , Leutert Mario , Dionne Ugo , Chang Alexis , Villén Judit , Landry Christian R 
Published: September 2024

AbstractThe fidelity of signal transduction requires the binding of regulatory molecules to their cognate targets. However, the crowded cell interior risks off-target interactions between proteins that are functionally unrelated. How such off-target interactions impact fitness is not generally known. Here, we use Saccharomyces cerevisiae to inducibly express tyrosine kinases. Because yeast lacks bona fide tyrosine kinases, the resulting tyrosine phosphorylation is biologically spurious. We engineered 44 yeast strains each expressing a tyrosine kinase, and quantitatively analysed their phosphoproteomes. This analysis resulted in ~30,000 phosphosites mapping to ~3500 proteins. The number of spurious pY sites generated correlates strongly with decreased growth, and we predict over 1000 pY events to be deleterious. However, we also find that many of the spurious pY sites have a negligible effect on fitness, possibly because of their low stoichiometry. This result is consistent with our evolutionary analyses demonstrating a lack of phosphotyrosine counter-selection in species with tyrosine kinases. Our results suggest that, alongside the risk for toxicity, the cell can tolerate a large degree of non-functional crosstalk as interaction networks evolve.