bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential
Authors: Koh Choong-Hyun , Lee Suyoung , Kwak Minkyeong , Kim Byung-Seok , Chung Yeonseok 
Published: November 2023

AbstractCD8 T cells play crucial roles in immune surveillance and defense against infections and cancer. After encountering antigenic stimulation, naïve CD8 T cells differentiate and acquire effector functions, enabling them to eliminate infected or malignant cells. Traditionally, cytotoxic T cells, characterized by their ability to produce effector cytokines and release cytotoxic granules to directly kill target cells, have been recognized as the constituents of the predominant effector T-cell subset. However, emerging evidence suggests distinct subsets of effector CD8 T cells that each exhibit unique effector functions and therapeutic potential. This review highlights recent advancements in our understanding of CD8 T-cell subsets and the contributions of these cells to various disease pathologies. Understanding the diverse roles and functions of effector CD8 T-cell subsets is crucial to discern the complex dynamics of immune responses in different disease settings. Furthermore, the development of immunotherapeutic approaches that specifically target and regulate the function of distinct CD8 T-cell subsets holds great promise for precision medicine.
IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis
Authors: Liang Li , Zhang Fengmei , Feng Naibo , Kuang Biao , Fan Mengtian , Chen Cheng , Pan Yiming , Zhou Pengfei , Geng Nana , Li Xingyue , Xian Menglin , Deng Lin , Li Xiaoli , Kuang Liang , Luo Fengtao , Tan Qiaoyan , Xie Yangli , Guo Fengjin 
Published: November 2023

AbstractOsteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.
Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentation facilitates multi-cancer early detection
Authors: Kim Su Yeon , Jeong Seongmun , Lee Wookjae , Jeon Yujin , Kim Yong-Jin , Park Seowoo , Lee Dongin , Go Dayoung , Song Sang-Hyun , Lee Sanghoo , Woo Hyun Goo , Yoon Jung-Ki , Park Young Sik , Kim Young Tae , Lee Se-Hoon , Kim Kwang Hyun , Lim Yoojoo , Kim Jin-Soo , Kim Hwang-Phill , Bang Duhee , Kim Tae-You 
Published: November 2023

AbstractCell-free DNA (cfDNA) sequencing has demonstrated great potential for early cancer detection. However, most large-scale studies have focused only on either targeted methylation sites or whole-genome sequencing, limiting comprehensive analysis that integrates both epigenetic and genetic signatures. In this study, we present a platform that enables simultaneous analysis of whole-genome methylation, copy number, and fragmentomic patterns of cfDNA in a single assay. Using a total of 950 plasma (361 healthy and 589 cancer) and 240 tissue samples, we demonstrate that a multifeature cancer signature ensemble (CSE) classifier integrating all features outperforms single-feature classifiers. At 95.2% specificity, the cancer detection sensitivity with methylation, copy number, and fragmentomic models was 77.2%, 61.4%, and 60.5%, respectively, but sensitivity was significantly increased to 88.9% with the CSE classifier (p value < 0.0001). For tissue of origin, the CSE classifier enhanced the accuracy beyond the methylation classifier, from 74.3% to 76.4%. Overall, this work proves the utility of a signature ensemble integrating epigenetic and genetic information for accurate cancer detection.
Filamentous virus-like particles are present in coral dinoflagellates across genera and ocean basins
Authors: Howe-Kerr Lauren I , Knochel Anna M , Meyer Matthew D , Sims Jordan A , Karrick Carly E , Grupstra Carsten G B , Veglia Alex J , Thurber Andrew R , Vega Thurber Rebecca L , Correa Adrienne M S 
Published: November 2023

Abstract
Filamentous viruses are hypothesized to play a role in stony coral tissue loss disease (SCTLD) through infection of the endosymbiotic dinoflagellates (Family Symbiodiniaceae) of corals. To evaluate this hypothesis, it is critical to understand the global distribution of filamentous virus infections across the genetic diversity of Symbiodiniaceae hosts. Using transmission electron microscopy, we demonstrate that filamentous virus-like particles (VLPs) are present in over 60% of Symbiodiniaceae cells (genus Cladocopium) within Pacific corals (Acropora hyacinthus, Porites c.f. lobata); these VLPs are more prevalent in Symbiodiniaceae of in situ colonies experiencing heat stress. Symbiodiniaceae expelled from A. hyacinthus also contain filamentous VLPs, and these cells are more degraded than their in hospite counterparts. Similar to VLPs reported from SCTLD-affected Caribbean reefs, VLPs range from ~150 to 1500 nm in length and 16–37 nm in diameter and appear to constitute various stages in a replication cycle. Finally, we demonstrate that SCTLD-affected corals containing filamentous VLPs are dominated by diverse Symbiodiniaceae lineages from the genera Breviolum, Cladocopium, and Durusdinium. Although this study cannot definitively confirm or refute the role of filamentous VLPs in SCTLD, it demonstrates that filamentous VLPs are not solely observed in SCTLD-affected corals or reef regions, nor are they solely associated with corals dominated by members of a particular Symbiodiniaceae genus. We hypothesize that filamentous viruses are a widespread, common group that infects Symbiodiniaceae. Genomic characterization of these viruses and empirical tests of the impacts of filamentous virus infection on Symbiodiniaceae and coral colonies should be prioritized.
Relationship of Klotho with cognition and dementia: Results from the NHANES 2011–2014 and Mendelian randomization study
Authors: Wu Yue , Lei Shaoyuan , Li Dongxiao , Li Zhongzhong , Zhang Yingzhen , Guo Yansu 
Published: November 2023

AbstractThe relationships of Klotho levels with cognition and dementia are poorly understood. This study aimed to investigate the association between Klotho levels and cognitive function and to determine causality between Klotho and dementia using Mendelian randomization (MR). Based on data from the National Health and Nutrition Survey (NHANES) 2011–2014, this study consisted of 1875 older adults aged 60–79 years. Cognitive function was assessed by the digit symbol substitution test (DSST). We performed weighted multivariable-adjusted linear regression to assess the association between Klotho concentrations and cognitive function. Then, 2-sample MR was conducted to assess the causal relationship between Klotho and dementia. The inverse variance weighted (IVW) method was used as the primary analysis. We observed a positive association between serum Klotho concentrations and the results of the Digit Symbol Substitution test (DSST) (T2: β 2.16, 95% CI: 0.30–4.01, P = 0.03, T3: β 2.48, 95% CI: 0.38–4.57, P = 0.02) after adjusting for the covariates. Moreover, there was also a potential nonlinear relationship between Klotho and DSST. The IVW method showed that genetically predicted high Klotho levels were not significantly associate with any type of dementia, including Alzheimer’s disease (OR = 1.03, 95% CI: 0.96–1.10, P = 0.46), vascular dementia (OR = 1.04, 95% CI: 0.87–1.25, P = 0.66), frontotemporal dementia (OR = 0.73, 95% CI: 0.47–1.14, P = 0.16), or dementia with Lewy bodies (OR = 1.03, 95% CI: 0.87–1.23, P = 0.73). In the cross-sectional observational study, Klotho and cognitive function were significantly correlated; however, findings from MR studies did not indicate a causal relationship between Klotho and dementia.
METTL3-mediated m6A methylation of C1qA regulates the Rituximab resistance of diffuse large B-cell lymphoma cells
Authors: Li Junping , Zhu Zhigang , Zhu Yuan , Li Jinqing , Li Kangbao , Zhong Weijie 
Published: November 2023

AbstractRituximab has been incorporated into the standard treatment regimen for diffuse large B-cell lymphoma (DLBCL), and induces the death of tumor cells via complement-dependent cytotoxicity (CDC). Unfortunately, the resistance of DLBCL cells to Rituximab limits its clinical usefulness. It remains unclear whether the complement system is related to Rituximab resistance in DLBCL. A Rituximab-resistant DLBCL cell line (Farage/R) was generated under the stress of Rituximab. Constituent proteins of the complement system in wild-type Farage cells (Farage/S) and Farage/R cells were analyzed by qPCR, western blotting, and immunofluorescence. In vitro and in vivo knockdown and overexpression studies confirmed that the complement 1Q subcomponent A chain (C1qA) was a regulator of Rituximab resistance. Finally, the mechanism by which C1qA is regulated by m6A methylation was explored. The reader and writer were identified by pull-down studies and RIP-qPCR. Activity of the complement system in Farage/R cells was suppressed. C1qA expression was reduced in Farage/R cells due to post-transcriptional regulation. Furthermore, in vitro and in vivo results showed that C1qA knockdown in Farage/S cells decreased their sensitivity to Rituximab, and C1qA overexpression in Farage/R cells attenuated the Rituximab resistance of those cells. Moreover, METTL3 and YTHDF2 were proven to be the reader and writer for m6A methylation of C1qA, respectively. Knockdown of METTL3 or YTHDF2 in Farage/R cells up-regulated C1qA expression and reduced their resistance to Rituximab. In summary, the aberrant downregulation of C1qA was related to Rituximab resistance in DLBCL cells, and C1qA was found to be regulated by METTL3- and YTHDF2-mediated m6A methylation. Enhancing the response of the complement system via regulation of C1qA might be an effective strategy for inhibiting Rituximab resistance in DLBCL.
Effects of socioeconomic status and race on survival and treatment in metastatic breast cancer
Authors: Puthanmadhom Narayanan Susrutha , Ren Dianxu , Oesterreich Steffi , Lee Adrian V. , Rosenzweig Margaret Q. , Brufsky Adam M. 
Published: November 2023

AbstractRace and socioeconomic factors affect outcomes in breast cancer. We aimed to assess the effect of race and neighborhood socioeconomic status (SES) on overall survival and treatment patterns in patients with metastatic breast cancer (MBC). This is a retrospective cohort study involving patients (N = 1246) with distant breast cancer metastases diagnosed at UPMC Magee Women’s Breast Cancer Clinic from 2000–2017. Overall survival and treatment patterns were compared between races (Blacks and whites) and SES groups (defined using Area Deprivation Index). Low SES, but not tumor characteristics, was associated with Black race (P < 0.001) in the study population. Low SES (Median [Interquartile Range, IQR] survival 2.3[2.2–2.5] years vs high SES 2.7[2.5–3.1] years,P = 0.01) and Black race (Median [IQR] survival 1.8[1.3–2.3] years, vs white 2.5[2.3–2.7] yearsP = 0.008) separately were associated with worse overall survival in patients with MBC. In the Cox Proportional Hazard model with SES, race, age, subtype, number of metastases, visceral metastasis, and year of diagnosis as covariates, low SES (Hazard ratio 1.19[1.04–1.35],P = 0.01), but not Black race (Hazard ratio 1.19[0.96–1.49],P = 0.12), independently predicted overall survival in MBC. Moreover, patients from low SES neighborhoods and Black race received fewer lines of chemotherapy than high SES and whites. In conclusion, low neighborhood SES is associated with worse outcomes in patients with MBC. Poor outcomes in Black patients with MBC, at least in part is driven by socioeconomic factors. Future studies should delineate the interplay between neighborhood SES, race, and their effects on tumor biology in MBC.
Efficacy and safety in mice of repeated, lifelong administration of an ANGPTL3 vaccine
Authors: Fukami Hirotaka , Morinaga Jun , Nakagami Hironori , Hayashi Hiroki , Okadome Yusuke , Matsunaga Eiji , Kadomatsu Tsuyoshi , Horiguchi Haruki , Sato Michio , Sugizaki Taichi , Miyata Keishi , Torigoe Daisuke , Mukoyama Masashi , Morishita Ryuichi , Oike Yuichi 
Published: November 2023

AbstractPreviously, we reported that an ANGPTL3 vaccine is a hopeful therapeutic option against dyslipidemia. In our current study, we assess durability and booster effects of that vaccine over a period representing a mouse’s lifespan. The vaccine remained effective for over one year, and booster vaccination maintained suppression of circulating triglyceride levels thereafter without major adverse effects on lungs, kidneys, or liver, suggesting vaccine efficacy and safety.
Efficient removal of aromatic pollutants via catalytic wet peroxide oxidation over synthetic anisotropic ilmenite/carbon nanocomposites
Authors: Guo Sheng , Huang Ran , Yuan Jia , Chen Rong , Chen Fengxi 
Published: November 2023

AbstractAs one of the most common ferrous (Fe2+)-containing oxide minerals in the Earth’s crust, ilmenite (FeTiO3) is a potential low-cost heterogeneous Fenton-like catalyst for organic wastewater treatment via catalytic wet peroxide oxidation (CWPO). However, it suffers from low activity and long induction time. Herein anisotropic FeTiO3/C nanocomposite with rich Fe2+ ions on large surface area of 159.0 m2 g−1 (surface Fe/Ti and Fe2+/Fe3+ ratios were respectively 2.1 and 2.0) was prepared via cetyltrimethylammonium (CTA+)-assisted sol-gel synthesis. CTA+ modulated the growth of FeTiO3 nanoparticles with more exposed metallic sites by preferential adsorption on its (104) plane via electrostatic attraction, provided the carbon source and facilitated the generation of more Fe2+ ions at the interface of FeTiO3/C via carbothermal reduction of FeTiO3. FeTiO3/C efficiently catalyzed CWPO removal of six aromatic pollutants with different charges (25 mg L−1 each) at 25 oC and pH 3.0 without an induction period owing to rich Fe2+ content on neutral surface (pHpzc ~3.3)—three dye solutions completely decolorized in 1 h and three antibiotics degraded by >90% in 3 h. Reusability of FeTiO3/C was demonstrated with cationic rhodamine B and anionic orange G dyes in five consecutive runs. Scavenging tests and spin-trapping EPR spectra confirmed the generation of dominant ·OH and minor O2•− species for organic degradation via catalytic decomposition of H2O2 on FeTiO3/C as a heterogeneous Fenton-like catalyst.
Structure of the native myosin filament in the relaxed cardiac sarcomere
Authors: Tamborrini Davide , Wang Zhexin , Wagner Thorsten , Tacke Sebastian , Stabrin Markus , Grange Michael , Kho Ay Lin , Rees Martin , Bennett Pauline , Gautel Mathias , Raunser Stefan 
Published: November 2023

AbstractThe thick filament is a key component of sarcomeres, the basic units of striated muscle1. Alterations in thick filament proteins are associated with familial hypertrophic cardiomyopathy and other heart and muscle diseases2. Despite the central importance of the thick filament, its molecular organization remains unclear. Here we present the molecular architecture of native cardiac sarcomeres in the relaxed state, determined by cryo-electron tomography. Our reconstruction of the thick filament reveals the three-dimensional organization of myosin, titin and myosin-binding protein C (MyBP-C). The arrangement of myosin molecules is dependent on their position along the filament, suggesting specialized capacities in terms of strain susceptibility and force generation. Three pairs of titin-α and titin-β chains run axially along the filament, intertwining with myosin tails and probably orchestrating the length-dependent activation of the sarcomere. Notably, whereas the three titin-α chains run along the entire length of the thick filament, titin-β chains do not. The structure also demonstrates that MyBP-C bridges thin and thick filaments, with its carboxy-terminal region binding to the myosin tails and directly stabilizing the OFF state of the myosin heads in an unforeseen manner. These results provide a foundation for future research investigating muscle disorders involving sarcomeric components.
Genome-wide epigenetic modifications in sports horses during training as an adaptation phenomenon
Authors: Cappelli Katia , Mecocci Samanta , Porceddu Andrea , Albertini Emidio , Giontella Andrea , Miglio Arianna , Silvestrelli Maurizio , Verini Supplizi Andrea , Marconi Gianpiero , Capomaccio Stefano 
Published: November 2023

AbstractWith his bicentennial breeding history based on athletic performance, the Thoroughbred horse can be considered the equine sport breed. Although genomic and transcriptomic tools and knowledge are at the state of the art in equine species, the epigenome and its modifications in response to environmental stimuli, such as training, are less studied. One of the major epigenetic modifications is cytosine methylation at 5′ of DNA molecules. This crucial biochemical modification directly mediates biological processes and, to some extent, determines the organisms' phenotypic plasticity. Exercise indeed affects the epigenomic state, both in humans and in horses. In this study, we highlight, with a genome-wide analysis of methylation, how the adaptation to training in the Thoroughbred can modify the methylation pattern throughout the genome. Twenty untrained horses, kept under the same environmental conditions and sprint training regimen, were recruited, collecting peripheral blood at the start of the training and after 30 and 90 days. Extracted leukocyte DNA was analyzed with the methylation content sensitive enzyme ddRAD (MCSeEd) technique for the first time applied to animal cells. Approximately one thousand differently methylated genomic regions (DMRs) and nearby genes were called, revealing that methylation changes can be found in a large part of the genome and, therefore, referable to the physiological adaptation to training. Functional analysis via GO enrichment was also performed. We observed significant differences in methylation patterns throughout the training stages: we hypothesize that the methylation profile of some genes can be affected early by training, while others require a more persistent stimulus.
A smartphone- and wearable-based biomarker for the estimation of unipolar depression severity
Authors: Zhuparris Ahnjili , Maleki Ghobad , van Londen Liesbeth , Koopmans Ingrid , Aalten Vincent , Yocarini Iris E. , Exadaktylos Vasileios , van Hemert Albert , Cohen Adam , Gal Pim , Doll Robert-Jan , Groeneveld Geert Jan , Jacobs Gabriël , Kraaij Wessel 
Published: November 2023

AbstractDrug development for mood disorders can greatly benefit from the development of robust, reliable, and objective biomarkers. The incorporation of smartphones and wearable devices in clinical trials provide a unique opportunity to monitor behavior in a non-invasive manner. The objective of this study is to identify the correlations between remotely monitored self-reported assessments and objectively measured activities with depression severity assessments often applied in clinical trials. 30 unipolar depressed patients and 29 age- and gender-matched healthy controls were enrolled in this study. Each participant’s daily physiological, physical, and social activity were monitored using a smartphone-based application (CHDR MORE™) for 3 weeks continuously. Self-reported depression anxiety stress scale-21 (DASS-21) and positive and negative affect schedule (PANAS) were administered via smartphone weekly and daily respectively. The structured interview guide for the Hamilton depression scale and inventory of depressive symptomatology–clinical rated (SIGHD-IDSC) was administered in-clinic weekly. Nested cross-validated linear mixed-effects models were used to identify the correlation between the CHDR MORE™ features with the weekly in-clinic SIGHD-IDSC scores. The SIGHD-IDSC regression model demonstrated an explained variance (R2) of 0.80, and a Root Mean Square Error (RMSE) of ± 15 points. The SIGHD-IDSC total scores were positively correlated with the DASS and mean steps-per-minute, and negatively correlated with the travel duration. Unobtrusive, remotely monitored behavior and self-reported outcomes are correlated with depression severity. While these features cannot replace the SIGHD-IDSC for estimating depression severity, it can serve as a complementary approach for assessing depression and drug effects outside the clinic.
Entropy in scalp EEG can be used as a preimplantation marker for VNS efficacy
Authors: Sklenarova B. , Chladek J. , Macek M. , Brazdil M. , Chrastina J. , Jurkova T. , Burilova P. , Plesinger F. , Zatloukalova E. , Dolezalova I. 
Published: November 2023

AbstractVagus nerve stimulation (VNS) is a therapeutic option in drug-resistant epilepsy. VNS leads to ≥ 50% seizure reduction in 50 to 60% of patients, termed "responders". The remaining 40 to 50% of patients, "non-responders", exhibit seizure reduction < 50%. Our work aims to differentiate between these two patient groups in preimplantation EEG analysis by employing several Entropy methods. We identified 59 drug-resistant epilepsy patients treated with VNS. We established their response to VNS in terms of responders and non-responders. A preimplantation EEG with eyes open/closed, photic stimulation, and hyperventilation was found for each patient. The EEG was segmented into eight time intervals within four standard frequency bands. In all, 32 EEG segments were obtained. Seven Entropy methods were calculated for all segments. Subsequently, VNS responders and non-responders were compared using individual Entropy methods. VNS responders and non-responders differed significantly in all Entropy methods except Approximate Entropy. Spectral Entropy revealed the highest number of EEG segments differentiating between responders and non-responders. The most useful frequency band distinguishing responders and non-responders was the alpha frequency, and the most helpful time interval was hyperventilation and rest 4 (the end of EEG recording).