bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability
Authors: Rosier Bob T. , Johnston William , Carda-Diéguez Miguel , Simpson Annabel , Cabello-Yeves Elena , Piela Krystyna , Reilly Robert , Artacho Alejandro , Easton Chris , Burleigh Mia , Culshaw Shauna , Mira Alex 
Published: January 2024

AbstractThe reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity (NRC) and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate (a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15 healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment (P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria (P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.
Ultra-simplified diffraction-based computational spectrometer
Authors: Chen Chuangchuang , Gu Honggang , Liu Shiyuan 
Published: January 2024

AbstractMiniaturizing spectrometers for compact and cost-effective mobile platforms is a major challenge in current spectroscopy research, where conventional spectrometers are impractical due to their bulky footprint. Existing miniaturized designs primarily rely on precalibrated response functions of nanophotonic structures to encode spectral information captured in a snapshot by detector arrays. Accurate spectrum reconstruction is achieved through computational techniques, but this requires precise component design, high-precision fabrication, and calibration. We propose an ultra-simplified computational spectrometer that employs a one-to-broadband diffraction decomposition strategy facilitated by a numerical regularized transform that depends only on the spectrum of the diffracted radiation. The key feature of our design is the use of a simple, arbitrarily shaped pinhole as the partial disperser, eliminating the need for complex encoding designs and full spectrum calibration. Our spectrometer achieves a reconstructed spectral peak location accuracy of better than 1 nm over a 200 nm bandwidth and excellent resolution for peaks separated by 3 nm in a bimodal spectrum, all within a compact footprint of under half an inch. Notably, our approach also reveals a breakthrough in broadband coherent diffractive imaging without requiring any prior knowledge of the broadband illumination spectrum, assumptions of non-dispersive specimens, or correction for detector quantum efficiency.
Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization
Authors: Okada Naohiro , Yahata Noriaki , Koshiyama Daisuke , Morita Kentaro , Sawada Kingo , Kanata Sho , Fujikawa Shinya , Sugimoto Noriko , Toriyama Rie , Masaoka Mio , Koike Shinsuke , Araki Tsuyoshi , Kano Yukiko , Endo Kaori , Yamasaki Syudo , Ando Shuntaro , Nishida Atsushi , Hiraiwa-Hasegawa Mariko , Edden Richard A. E. , Sawa Akira , Kasai Kiyoto 
Published: January 2024

AbstractPrevious studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.
Inhibition of the YAP-MMB interaction and targeting NEK2 as potential therapeutic strategies for YAP-driven cancers
Authors: Jessen Marco , Gertzmann Dörthe , Liss Franziska , Zenk Franziska , Bähner Laura , Schöffler Victoria , Schulte Clemens , Maric Hans Michael , Ade Carsten P. , von Eyss Björn , Gaubatz Stefan 
Published: January 2024

AbstractYAP activation in cancer is linked to poor outcomes, making it an attractive therapeutic target. Previous research focused on blocking the interaction of YAP with TEAD transcription factors. Here, we took a different approach by disrupting YAP’s binding to the transcription factor B-MYB using MY-COMP, a fragment of B-MYB containing the YAP binding domain fused to a nuclear localization signal. MY-COMP induced cell cycle defects, nuclear abnormalities, and polyploidization. In an AKT and YAP-driven liver cancer model, MY-COMP significantly reduced liver tumorigenesis, highlighting the importance of the YAP-B-MYB interaction in tumor development. MY-COMP also perturbed the cell cycle progression of YAP-dependent uveal melanoma cells but not of YAP-independent cutaneous melanoma cell lines. It counteracted YAP-dependent expression of MMB-regulated cell cycle genes, explaining the observed effects. We also identified NIMA-related kinase (NEK2) as a downstream target of YAP and B-MYB, promoting YAP-driven transformation by facilitating centrosome clustering and inhibiting multipolar mitosis.
TREM2 macrophage promotes cardiac repair in myocardial infarction by reprogramming metabolism via SLC25A53
Authors: Gong Shiyu , Zhai Ming , Shi Jiayun , Yu Guanye , Lei Zhijun , Shi Yefei , Zeng Yanxi , Ju Peinan , Yang Na , Zhang Zhuo , Zhang Donghui , Zhuang Jianhui , Yu Qing , Zhang Xumin , Jian Weixia , Wang Wei , Peng Wenhui 
Published: January 2024

AbstractEfferocytosis and metabolic reprogramming of macrophages play crucial roles in myocardial infarction (MI) repair. TREM2 has been proven to participate in phagocytosis and metabolism, but how it modulates myocardial infarction remains unclear. In this study, we showed that macrophage-specific TREM2 deficiency worsened cardiac function and impaired post-MI repair. Using RNA-seq, protein and molecular docking, and Targeted Metabolomics (LC–MS), our data demonstrated that macrophages expressing TREM2 exhibited decreased SLC25A53 transcription through the SYK-SMAD4 signaling pathway after efferocytosis, which impaired NAD+ transport into mitochondria, downregulated SLC25A53 thereby causing the breakpoint in the TCA cycle and subsequently increased itaconate production. In vitro experiments confirmed that itaconate secreted by TREM2+ macrophages inhibited cardiomyocyte apoptosis and promoted fibroblast proliferation. Conversely, overexpression of TREM2 in macrophages could improve cardiac function. In summary, our study reveals a novel role for macrophage-specific TREM2 in MI, connecting efferocytosis to immune metabolism during cardiac repair.
FUNDC1-induced mitophagy protects spinal cord neurons against ischemic injury
Authors: Chen Dehui , Zhou Linquan , Chen Gang , Lin Taotao , Lin Jiemin , Zhao Xin , Li Wenwen , Guo Shengyu , Wu Rongcan , Wang Zhenyu , Liu Wenge 
Published: January 2024

AbstractLocal ischemia and hypoxia are the most important pathological processes in the early phase of secondary spinal cord injury (SCI), in which mitochondria are the main target of ischemic injury. Mitochondrial autophagy, also known as mitophagy, acts as a selective autophagy that specifically identifies and degrades damaged mitochondria, thereby reducing mitochondria-dependent apoptosis. Accumulating evidence shows that the mitophagy receptor, FUN14 domain-containing 1 (FUNDC1), plays an important role in ischemic injury, but the role of FUNDC1 in SCI has not been reported. In this study, we aimed to investigate whether FUNDC1 can enhance mitophagy and inhibit neuronal apoptosis in the early stage of SCI. In a rat SCI model, we found that FUNDC1 overexpression enhanced neuronal autophagy and decreased neuronal apoptosis in the early stage of injury, thereby reducing spinal cord damage. In vitro studies showed that the neuroprotective effects of FUNDC1 were achieved by inhibiting mitochondria-dependent apoptosis and improving mitochondrial function. In addition, FUNDC1 enhanced mitophagy. The protective effects of FUNDC1 against apoptosis and mitochondrial dysfunction were reversed by 3-methyladenine (3-MA), an autophagy inhibitor. Taken together, our results confirm that FUNDC1 can protect against neuronal loss after SCI by inducing mitophagy, inhibiting mitochondria-dependent apoptosis, and improving mitochondrial function.
A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways
Authors: Zhang Zhibin , Lin Xi , Wei Ling , Wu Yiran , Xu Lu , Wu Lijie , Wei Xiaohu , Zhao Suwen , Zhu Xiangjia , Xu Fei 
Published: January 2024

AbstractThe ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.
Is food insecurity associated with dental caries?
Authors: Holmes Richard D. 
Published: January 2024

Abstract
Data sources
Eight electronic databases including APA PsycINFO, CINAHL, Embase, LILACS, PubMed, Ovid, Scopus and Web of Science were searched from date of inception to November 2021. An updated search was conducted in August 2022. Google Scholar was accessed including Open Grey and ProQuest. Reference lists of the included studies were analysed for potentially eligible studies.

Study selection
Observational studies (cross-sectional, case-control and cohort) that evaluated the association between dental caries and food insecurity were eligible for analysis. Qualitative studies, reviews and meeting abstracts were excluded. There were no restrictions on language or publication date.

Data extraction and synthesis
Two reviewers independently screened titles and abstracts. A third experienced researcher was consulted if there was disagreement. Food insecurity status was the exposure with dental caries the outcome. The authors retrieved effect measures, 95% CI’s and P values where available. Heterogeneity was assessed via I2 and R2. A total of 514 records were initially identified. Once duplicates were removed, 19 references were assessed in full. The association between food insecurity and dental caries were presented as odds-ratios, relative risks and prevalence ratios with 95% CIs. A random-effects model was fitted to all meta-analyses.

Results
Evaluation identified 14 studies for the qualitative synthesis and 7 studies for the quantitative synthesis. The total sample size for the 14 studies was 150,546 individuals. Quantitative data merged from two studies found food-insecure individuals more prone to dental caries than food-secure individuals (OR = 1.62; 95% CI, 1.01–2.60; P = 0.045). In two studies that used binary data to compare food security or insecurity, food insecure individuals were more likely to exhibit dental caries (OR = 1.66; 95% CI, 1.36–2.02; P < 0.0001).

Conclusions
People experiencing food insecurity are more likely to exhibit dental caries than those who have food security.
A novel DLG4 variant causes DLG4-related synaptopathy with intellectual regression
Authors: Tokunaga Sachi , Shimomura Hideki , Taniguchi Naoko , Yanagi Kumiko , Kaname Tadashi , Okamoto Nobuhiko , Takeshima Yasuhiro 
Published: January 2024

Abstract

DLG4-related synaptopathy is a neurodevelopmental disorder caused by a DLG4 variant. We identified a novel de novo heterozygous frameshift variant, NM_001321075.3(DLG4):c.554_563del, in a Japanese girl. Intellectual regression without motor delay was observed at 2 years of age, and she was diagnosed with autism spectrum disorder and attention-deficit/hyperactivity disorder. Recognizing the possibility of DLG4-related synaptopathy in patients with intellectual regression is important for ensuring an accurate diagnosis.
Boosting with adjuvanted SCB-2019 elicits superior Fcγ-receptor engagement driven by IgG3 to SARS-CoV-2 spike
Authors: Jung Wonyeong , Yuan Dansu , Kellman Benjamin , Gonzalez Isabela Garrido da Silva , Clemens Ralf , Milan Eveline Pipolo , Sprinz Eduardo , Cerbino Neto José , Smolenov Igor , Alter Galit , McNamara Ryan P. , Costa Clemens Sue Ann 
Published: January 2024

AbstractWith the continued emergence of variants of concern, the global threat of COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at a low cost while antigen design and adjuvant use can modulate efficacy and safety. While effective humoral immunity against SARS-CoV-2 variants has been shown to depend on both neutralization and Fc-mediated immunity, data on the effectiveness of protein-based vaccines with enhanced Fc-mediated immunity is limited. Here, we assess the humoral profile, including antibody isotypes, subclasses, and Fc receptor binding generated by a boosting with a recombinant trimer-tag protein vaccine SCB-2019. Individuals who were primed with 2 doses of the ChAdOx1 vaccine were equally divided into 4 groups and boosted with following formulations: Group 1: 9 μg SCB-2019 and Alhydrogel; Group 2: 9 μg SCB-2019, CpG 1018, and Alhydrogel; Group 3: 30 μg SCB-2019, CpG 1018, and Alhydrogel; Group 4: ChAdOx1. Group 3 showed enhanced antibody FcγR binding against wild-type and variants compared to Groups 1 and 2, showing a dose-dependent enhancement of immunity conferred by the SCB-2019 vaccine. Moreover, from day 15 after vaccination, Group 3 exhibited higher IgG3 and FcγR binding across variants of concerns, including Omicron and its subvariants, compared to the ChAdOx1-boosted individuals. Overall, this highlights the potential of SCB-2019 as a cost-efficient boosting regimen effective across variants of concerns.
Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation
Authors: Bravo González-Blas Carmen , Matetovici Irina , Hillen Hanne , Taskiran Ibrahim Ihsan , Vandepoel Roel , Christiaens Valerie , Sansores-García Leticia , Verboven Elisabeth , Hulselmans Gert , Poovathingal Suresh , Demeulemeester Jonas , Psatha Nikoleta , Mauduit David , Halder Georg , Aerts Stein 
Published: January 2024

AbstractIn the mammalian liver, hepatocytes exhibit diverse metabolic and functional profiles based on their location within the liver lobule. However, it is unclear whether this spatial variation, called zonation, is governed by a well-defined gene regulatory code. Here, using a combination of single-cell multiomics, spatial omics, massively parallel reporter assays and deep learning, we mapped enhancer-gene regulatory networks across mouse liver cell types. We found that zonation affects gene expression and chromatin accessibility in hepatocytes, among other cell types. These states are driven by the repressors TCF7L1 and TBX3, alongside other core hepatocyte transcription factors, such as HNF4A, CEBPA, FOXA1 and ONECUT1. To examine the architecture of the enhancers driving these cell states, we trained a hierarchical deep learning model called DeepLiver. Our study provides a multimodal understanding of the regulatory code underlying hepatocyte identity and their zonation state that can be used to engineer enhancers with specific activity levels and zonation patterns.
Distinct and shared genetic architectures of gestational diabetes mellitus and type 2 diabetes
Authors: Elliott Amanda , Walters Raymond K. , Pirinen Matti , Kurki Mitja , Junna Nella , Goldstein Jacqueline I. , Reeve Mary Pat , Siirtola Harri , Lemmelä Susanna M. , Turley Patrick , Lahtela Elisa , Mehtonen Juha , Reis Kadri , Elnahas Abdelrahman G. , Reigo Anu , Palta Priit , Esko Tõnu , Mägi Reedik ,   Estonian Biobank Research Team, Metspalu Andres , Nelis Mari , Milani Lili , Hudjashov Georgi ,   FinnGen, Siirtola Haari , Lahtinen Elisa , Palotie Aarno , Daly Mark J. , Widén Elisabeth 
Published: January 2024

AbstractGestational diabetes mellitus (GDM) is a common metabolic disorder affecting more than 16 million pregnancies annually worldwide1,2. GDM is related to an increased lifetime risk of type 2 diabetes (T2D)1–3, with over a third of women developing T2D within 15 years of their GDM diagnosis. The diseases are hypothesized to share a genetic predisposition1–7, but few studies have sought to uncover the genetic underpinnings of GDM. Most studies have evaluated the impact of T2D loci only8–10, and the three prior genome-wide association studies of GDM11–13 have identified only five loci, limiting the power to assess to what extent variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen study and identified 13 GDM-associated loci, including nine new loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into the following two distinct categories: one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis and placental expression.
Latent neural population dynamics underlying breathing, opioid-induced respiratory depression and gasping
Authors: Bush Nicholas Edward , Ramirez Jan-Marino 
Published: January 2024

AbstractBreathing is vital and must be concurrently robust and flexible. This rhythmic behavior is generated and maintained within a rostrocaudally aligned set of medullary nuclei called the ventral respiratory column (VRC). The rhythmic properties of individual VRC nuclei are well known, yet technical challenges have limited the interrogation of the entire VRC population simultaneously. Here we characterize over 15,000 medullary units using high-density electrophysiology, opto-tagging and histological reconstruction. Population dynamics analysis reveals consistent rotational trajectories through a low-dimensional neural manifold. These rotations are robust and maintained even during opioid-induced respiratory depression. During severe hypoxia-induced gasping, the low-dimensional dynamics of the VRC reconfigure from rotational to all-or-none, ballistic efforts. Thus, latent dynamics provide a unifying lens onto the activities of large, heterogeneous populations of neurons involved in the simple, yet vital, behavior of breathing, and well describe how these populations respond to a variety of perturbations.
The potential of epigenetic therapy to target the 3D epigenome in endocrine-resistant breast cancer
Authors: Achinger-Kawecka Joanna , Stirzaker Clare , Portman Neil , Campbell Elyssa , Chia Kee-Ming , Du Qian , Laven-Law Geraldine , Nair Shalima S. , Yong Aliza , Wilkinson Ashleigh , Clifton Samuel , Milioli Heloisa H. , Alexandrou Sarah , Caldon C. Elizabeth , Song Jenny , Khoury Amanda , Meyer Braydon , Chen Wenhan , Pidsley Ruth , Qu Wenjia , Gee Julia M. W. , Schmitt Anthony , Wong Emily S. , Hickey Theresa E. , Lim Elgene , Clark Susan J. 
Published: January 2024

AbstractThree-dimensional (3D) epigenome remodeling is an important mechanism of gene deregulation in cancer. However, its potential as a target to counteract therapy resistance remains largely unaddressed. Here, we show that epigenetic therapy with decitabine (5-Aza-mC) suppresses tumor growth in xenograft models of pre-clinical metastatic estrogen receptor positive (ER+) breast tumor. Decitabine-induced genome-wide DNA hypomethylation results in large-scale 3D epigenome deregulation, including de-compaction of higher-order chromatin structure and loss of boundary insulation of topologically associated domains. Significant DNA hypomethylation associates with ectopic activation of ER-enhancers, gain in ER binding, creation of new 3D enhancer–promoter interactions and concordant up-regulation of ER-mediated transcription pathways. Importantly, long-term withdrawal of epigenetic therapy partially restores methylation at ER-enhancer elements, resulting in a loss of ectopic 3D enhancer–promoter interactions and associated gene repression. Our study illustrates the potential of epigenetic therapy to target ER+ endocrine-resistant breast cancer by DNA methylation-dependent rewiring of 3D chromatin interactions, which are associated with the suppression of tumor growth.