bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus
Authors: Hashimoto Masashi , Kuroda Shinji , Kanaya Nobuhiko , Kadowaki Daisuke , Yoshida Yusuke , Sakamoto Masaki , Hamada Yuki , Sugimoto Ryoma , Yagi Chiaki , Ohtani Tomoko , Kumon Kento , Kakiuchi Yoshihiko , Yasui Kazuya , Kikuchi Satoru , Yoshida Ryuichi , Tazawa Hiroshi , Kagawa Shunsuke , Yagi Takahito , Urata Yasuo , Fujiwara Toshiyoshi 
Published: February 2024

Abstract
Background
Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).

Methods
We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).

Results
First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.

Conclusion
OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.
Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease
Authors: Walker Mary E. , De Matteis Roberta , Perretti Mauro , Dalli Jesmond 
Published: February 2024

AbstractWhile cardiovascular disease (CVD) is one of the major co-morbidities in patients with rheumatoid arthritis (RA), the mechanism(s) that contribute to CVD in patients with RA remain to be fully elucidated. Herein, we observe that plasma concentrations of 13-series resolvin (RvT)4 negatively correlate with vascular lipid load in mouse inflammatory arthritis. Administration of RvT4 to male arthritic mice fed an atherogenic diet significantly reduces atherosclerosis. Assessment of the mechanisms elicited by this mediator demonstrates that RvT4 activates cholesterol efflux in lipid laden macrophages via a Scavenger Receptor class B type 1 (SR-BI)-Neutral Cholesterol Ester Hydrolase-dependent pathway. This leads to the reprogramming of lipid laden macrophages yielding tissue protection. Pharmacological inhibition or knockdown of macrophage SR-BI reverses the vasculo-protective activities of RvT4 in vitro and in male mice in vivo. Together these findings elucidate a RvT4-SR-BI centered mechanism that orchestrates macrophage responses to limit atherosclerosis during inflammatory arthritis.
Health effects associated with chewing tobacco: a Burden of Proof study
Authors: Gil Gabriela F. , Anderson Jason A. , Aravkin Aleksandr , Bhangdia Kayleigh , Carr Sinclair , Dai Xiaochen , Flor Luisa S. , Hay Simon I. , Malloy Matthew J. , McLaughlin Susan A. , Mullany Erin C. , Murray Christopher J. L. , O’Connell Erin M. , Okereke Chukwuma , Sorensen Reed J. D. , Whisnant Joanna , Zheng Peng , Gakidou Emmanuela 
Published: February 2024

AbstractChewing tobacco use poses serious health risks; yet it has not received as much attention as other tobacco-related products. This study synthesizes existing evidence regarding the health impacts of chewing tobacco while accounting for various sources of uncertainty. We conducted a systematic review and meta-analysis of chewing tobacco and seven health outcomes, drawing on 103 studies published from 1970 to 2023. We use a Burden of Proof meta-analysis to generate conservative risk estimates and find weak-to-moderate evidence that tobacco chewers have an increased risk of stroke, lip and oral cavity cancer, esophageal cancer, nasopharynx cancer, other pharynx cancer, and laryngeal cancer. We additionally find insufficient evidence of an association between chewing tobacco and ischemic heart disease. Our findings highlight a need for policy makers, researchers, and communities at risk to devote greater attention to chewing tobacco by both advancing tobacco control efforts and investing in strengthening the existing evidence base.
Aneuploid embryonic stem cells drive teratoma metastasis
Authors: Xiao Rong , Xu Deshu , Zhang Meili , Chen Zhanghua , Cheng Li , Du Songjie , Lu Mingfei , Zhou Tonghai , Li Ruoyan , Bai Fan , Huang Yue 
Published: February 2024

AbstractAneuploidy, a deviation of the chromosome number from euploidy, is one of the hallmarks of cancer. High levels of aneuploidy are generally correlated with metastasis and poor prognosis in cancer patients. However, the causality of aneuploidy in cancer metastasis remains to be explored. Here we demonstrate that teratomas derived from aneuploid murine embryonic stem cells (ESCs), but not from isogenic diploid ESCs, disseminated to multiple organs, for which no additional copy number variations were required. Notably, no cancer driver gene mutations were identified in any metastases. Aneuploid circulating teratoma cells were successfully isolated from peripheral blood and showed high capacities for migration and organ colonization. Single-cell RNA sequencing of aneuploid primary teratomas and metastases identified a unique cell population with high stemness that was absent in diploid ESCs-derived teratomas. Further investigation revealed that aneuploid cells displayed decreased proteasome activity and overactivated endoplasmic reticulum (ER) stress during differentiation, thereby restricting the degradation of proteins produced from extra chromosomes in the ESC state and causing differentiation deficiencies. Noticeably, both proteasome activator Oleuropein and ER stress inhibitor 4-PBA can effectively inhibit aneuploid teratoma metastasis.
High-efficiency reinforcement learning with hybrid architecture photonic integrated circuit
Authors: Li Xuan-Kun , Ma Jian-Xu , Li Xiang-Yu , Hu Jun-Jie , Ding Chuan-Yang , Han Feng-Kai , Guo Xiao-Min , Tan Xi , Jin Xian-Min 
Published: February 2024

AbstractReinforcement learning (RL) stands as one of the three fundamental paradigms within machine learning and has made a substantial leap to build general-purpose learning systems. However, using traditional electrical computers to simulate agent-environment interactions in RL models consumes tremendous computing resources, posing a significant challenge to the efficiency of RL. Here, we propose a universal framework that utilizes a photonic integrated circuit (PIC) to simulate the interactions in RL for improving the algorithm efficiency. High parallelism and precision on-chip optical interaction calculations are implemented with the assistance of link calibration in the hybrid architecture PIC. By introducing similarity information into the reward function of the RL model, PIC-RL successfully accomplishes perovskite materials synthesis task within a 3472-dimensional state space, resulting in a notable 56% improvement in efficiency. Our results validate the effectiveness of simulating RL algorithm interactions on the PIC platform, highlighting its potential to boost computing power in large-scale and sophisticated RL tasks.
Avoiding ecosystem and social impacts of hydropower, wind, and solar in Southern Africa’s low-carbon electricity system
Authors: Wu Grace C. , Deshmukh Ranjit , Trainor Anne , Uppal Anagha , Chowdhury A. F. M. Kamal , Baez Carlos , Martin Erik , Higgins Jonathan , Mileva Ana , Ndhlukula Kudakwashe 
Published: February 2024

AbstractThe scale at which low-carbon electricity will need to be deployed to meet economic growth, electrification, and climate goals in Africa is unprecedented, yet the potential land use and freshwater impacts from this massive build-out of energy infrastructure is poorly understood. In this study, we characterize low-impact onshore wind, solar photovoltaics, and hydropower potential in Southern Africa and identify the cost-optimal mix of electricity generation technologies under different sets of socio-environmental land use and freshwater constraints and carbon targets. We find substantial wind and solar potential after applying land use protections, but about 40% of planned or proposed hydropower projects face socio-environmental conflicts. Applying land and freshwater protections results in more wind, solar, and battery capacity and less hydropower capacity compared to scenarios without protections. While a carbon target favors hydropower, the amount of cost-competitively selected hydropower is at most 45% of planned or proposed hydropower capacity in any scenario—and is only 25% under socio-environmental protections. Achieving both carbon targets and socio-environmental protections results in system cost increases of 3-6%. In the absence of land and freshwater protections, environmental and social impacts from new hydropower development could be significant.
G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis
Authors: Wang Wenmeng , Li Dangdang , Xu Qingqing , Cheng Jiahui , Yu Zhiwei , Li Guangyue , Qiao Shiyao , Pan Jiasong , Wang Hao , Shi Jinming , Zheng Tongsen , Sui Guangchao 
Published: February 2024

AbstractG-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.
Manipulating solvent fluidic dynamics for large-area perovskite film-formation and white light-emitting diodes
Authors: Shi Guangyi , Huang Zongming , Qiao Ran , Chen Wenjing , Li Zhijian , Li Yaping , Mu Kai , Si Ting , Xiao Zhengguo 
Published: February 2024

AbstractPresynthesized perovskite quantum dots are very promising for making films with different compositions, as they decouple crystallization and film-formation processes. However, fabricating large-area uniform films using perovskite quantum dots is still very challenging due to the complex fluidic dynamics of the solvents. Here, we report a robust film-formation approach using an environmental-friendly binary-solvent strategy. Nonbenzene solvents, n-octane and n-hexane, are mixed to manipulate the fluidic and evaporation dynamics of the perovskite quantum dot inks, resulting in balanced Marangoni flow, enhanced ink spreadability, and uniform solute-redistribution. We can therefore blade-coat large-area uniform perovskite films with different compositions using the same fabrication parameters. White and red perovskite light-emitting diodes incorporating blade-coated films exhibit a decent external quantum efficiency of 10.6% and 15.3% (0.04 cm2), and show a uniform emission up to 28 cm2. This work represents a significant step toward the application of perovskite light-emitting diodes in flat panel solid-state lighting.
SARS-CoV-2 vaccination may mitigate dysregulation of IL-1/IL-18 and gastrointestinal symptoms of the post-COVID-19 condition
Authors: Fischer Claudia , Willscher Edith , Paschold Lisa , Gottschick Cornelia , Klee Bianca , Diexer Sophie , Bosurgi Lidia , Dutzmann Jochen , Sedding Daniel , Frese Thomas , Girndt Matthias , Hoell Jessica I. , Gekle Michael , Addo Marylyn M. , Schulze zur Wiesch Julian , Mikolajczyk Rafael , Binder Mascha , Schultheiß Christoph 
Published: February 2024

AbstractThe rapid development of safe and effective vaccines helped to prevent severe disease courses after SARS-CoV-2 infection and to mitigate the progression of the COVID-19 pandemic. While there is evidence that vaccination may reduce the risk of developing post-COVID-19 conditions (PCC), this effect may depend on the viral variant. Therapeutic effects of post-infection vaccination have been discussed but the data for individuals with PCC remains inconclusive. In addition, extremely rare side effects after SARS-CoV-2 vaccination may resemble the heterogeneous PCC phenotype. Here, we analyze the plasma levels of 25 cytokines and SARS-CoV-2 directed antibodies in 540 individuals with or without PCC relative to one or two mRNA-based COVID-19 vaccinations as well as in 20 uninfected individuals one month after their initial mRNA-based COVID-19 vaccination. While none of the SARS-CoV-2 naïve individuals reported any persisting sequelae or exhibited PCC-like dysregulation of plasma cytokines, we detected lower levels of IL-1β and IL-18 in patients with ongoing PCC who received one or two vaccinations at a median of six months after infection as compared to unvaccinated PCC patients. This reduction correlated with less frequent reporting of persisting gastrointestinal symptoms. These data suggest that post-infection vaccination in patients with PCC might be beneficial in a subgroup of individuals displaying gastrointestinal symptoms.
A metabolite sensor subunit of the Atg1/ULK complex regulates selective autophagy
Authors: Gross A. S. , Ghillebert R. , Schuetter M. , Reinartz E. , Rowland A. , Bishop B. C. , Stumpe M. , Dengjel J. , Graef M. 
Published: February 2024

AbstractCells convert complex metabolic information into stress-adapted autophagy responses. Canonically, multilayered protein kinase networks converge on the conserved Atg1/ULK kinase complex (AKC) to induce non-selective and selective forms of autophagy in response to metabolic changes. Here we show that, upon phosphate starvation, the metabolite sensor Pho81 interacts with the adaptor subunit Atg11 at the AKC via an Atg11/FIP200 interaction motif to modulate pexophagy by virtue of its conserved phospho-metabolite sensing SPX domain. Notably, core AKC components Atg13 and Atg17 are dispensable for phosphate starvation-induced autophagy revealing significant compositional and functional plasticity of the AKC. Our data indicate that, instead of functioning as a selective autophagy receptor, Pho81 compensates for partially inactive Atg13 by promoting Atg11 phosphorylation by Atg1 critical for pexophagy during phosphate starvation. Our work shows Atg11/FIP200 adaptor subunits bind not only selective autophagy receptors but also modulator subunits that convey metabolic information directly to the AKC for autophagy regulation.
microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data
Authors: Zuffa Simone , Schmid Robin , Bauermeister Anelize , P. Gomes Paulo Wender , Caraballo-Rodriguez Andres M. , El Abiead Yasin , Aron Allegra T. , Gentry Emily C. , Zemlin Jasmine , Meehan Michael J. , Avalon Nicole E. , Cichewicz Robert H. , Buzun Ekaterina , Terrazas Marvic Carrillo , Hsu Chia-Yun , Oles Renee , Ayala Adriana Vasquez , Zhao Jiaqi , Chu Hiutung , Kuijpers Mirte C. M. , Jackrel Sara L. , Tugizimana Fidele , Nephali Lerato Pertunia , Dubery Ian A. , Madala Ntakadzeni Edwin , Moreira Eduarda Antunes , Costa-Lotufo Leticia Veras , Lopes Norberto Peporine , Rezende-Teixeira Paula , Jimenez Paula C. , Rimal Bipin , Patterson Andrew D. , Traxler Matthew F. , Pessotti Rita de Cassia , Alvarado-Villalobos Daniel , Tamayo-Castillo Giselle , Chaverri Priscila , Escudero-Leyva Efrain , Quiros-Guerrero Luis-Manuel , Bory Alexandre Jean , Joubert Juliette , Rutz Adriano , Wolfender Jean-Luc , Allard Pierre-Marie , Sichert Andreas , Pontrelli Sammy , Pullman Benjamin S. , Bandeira Nuno , Gerwick William H. , Gindro Katia , Massana-Codina Josep , Wagner Berenike C. , Forchhammer Karl , Petras Daniel , Aiosa Nicole , Garg Neha , Liebeke Manuel , Bourceau Patric , Kang Kyo Bin , Gadhavi Henna , de Carvalho Luiz Pedro Sorio , Silva dos Santos Mariana , Pérez-Lorente Alicia Isabel , Molina-Santiago Carlos , Romero Diego , Franke Raimo , Brönstrup Mark , Vera Ponce de León Arturo , Pope Phillip Byron , La Rosa Sabina Leanti , La Barbera Giorgia , Roager Henrik M. , Laursen Martin Frederik , Hammerle Fabian , Siewert Bianka , Peintner Ursula , Licona-Cassani Cuauhtemoc , Rodriguez-Orduña Lorena , Rampler Evelyn , Hildebrand Felina , Koellensperger Gunda , Schoeny Harald , Hohenwallner Katharina , Panzenboeck Lisa , Gregor Rachel , O’Neill Ellis Charles , Roxborough Eve Tallulah , Odoi Jane , Bale Nicole J. , Ding Su , Sinninghe Damsté Jaap S. , Guan Xue Li , Cui Jerry J. , Ju Kou-San , Silva Denise Brentan , Silva Fernanda Motta Ribeiro , da Silva Gilvan Ferreira , Koolen Hector H. F. , Grundmann Carlismari , Clement Jason A. , Mohimani Hosein , Broders Kirk , McPhail Kerry L. , Ober-Singleton Sidnee E. , Rath Christopher M. , McDonald Daniel , Knight Rob , Wang Mingxun , Dorrestein Pieter C. 
Published: February 2024

AbstractmicrobeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms’ role in ecology and human health.
Stepwise assembly and release of Tc toxins from Yersinia entomophaga
Authors: Feldmüller Miki , Ericson Charles F. , Afanasyev Pavel , Lien Yun-Wei , Weiss Gregor L. , Wollweber Florian , Schoof Marion , Hurst Mark , Pilhofer Martin 
Published: February 2024

AbstractTc toxins are virulence factors of bacterial pathogens. Although their structure and intoxication mechanism are well understood, it remains elusive where this large macromolecular complex is assembled and how it is released. Here we show by an integrative multiscale imaging approach that Yersinia entomophaga Tc (YenTc) toxin components are expressed only in a subpopulation of cells that are ‘primed’ with several other potential virulence factors, including filaments of the protease M66/StcE. A phage-like lysis cassette is required for YenTc release; however, before resulting in complete cell lysis, the lysis cassette generates intermediate ‘ghost’ cells, which may serve as assembly compartments and become packed with assembled YenTc holotoxins. We hypothesize that this stepwise mechanism evolved to minimize the number of cells that need to be killed. The occurrence of similar lysis cassettes in diverse organisms indicates a conserved mechanism for Tc toxin release that may apply to other extracellular macromolecular machines.
Deep learning-aided decision support for diagnosis of skin disease across skin tones
Authors: Groh Matthew , Badri Omar , Daneshjou Roxana , Koochek Arash , Harris Caleb , Soenksen Luis R. , Doraiswamy P. Murali , Picard Rosalind 
Published: February 2024

AbstractAlthough advances in deep learning systems for image-based medical diagnosis demonstrate their potential to augment clinical decision-making, the effectiveness of physician–machine partnerships remains an open question, in part because physicians and algorithms are both susceptible to systematic errors, especially for diagnosis of underrepresented populations. Here we present results from a large-scale digital experiment involving board-certified dermatologists (n = 389) and primary-care physicians (n = 459) from 39 countries to evaluate the accuracy of diagnoses submitted by physicians in a store-and-forward teledermatology simulation. In this experiment, physicians were presented with 364 images spanning 46 skin diseases and asked to submit up to four differential diagnoses. Specialists and generalists achieved diagnostic accuracies of 38% and 19%, respectively, but both specialists and generalists were four percentage points less accurate for the diagnosis of images of dark skin as compared to light skin. Fair deep learning system decision support improved the diagnostic accuracy of both specialists and generalists by more than 33%, but exacerbated the gap in the diagnostic accuracy of generalists across skin tones. These results demonstrate that well-designed physician–machine partnerships can enhance the diagnostic accuracy of physicians, illustrating that success in improving overall diagnostic accuracy does not necessarily address bias.
The palisade layer of the poxvirus core is composed of flexible A10 trimers
Authors: Liu Jiasui , Corroyer-Dulmont Simon , Pražák Vojtěch , Khusainov Iskander , Bahrami Karola , Welsch Sonja , Vasishtan Daven , Obarska-Kosińska Agnieszka , Thorkelsson Sigurdur R. , Grünewald Kay , Quemin Emmanuelle R. J. , Turoňová Beata , Locker Jacomina Krijnse 
Published: February 2024

AbstractDue to its asymmetric shape, size and compactness, the structure of the infectious mature virus (MV) of vaccinia virus (VACV), the best-studied poxvirus, remains poorly understood. Instead, subviral particles, in particular membrane-free viral cores, have been studied with cryo-electron microscopy. Here, we compared viral cores obtained by detergent stripping of MVs with cores in the cellular cytoplasm, early in infection. We focused on the prominent palisade layer on the core surface, combining cryo-electron tomography, subtomogram averaging and AlphaFold2 structure prediction. We showed that the palisade is composed of densely packed trimers of the major core protein A10. Trimers display a random order and their classification indicates structural flexibility. A10 on cytoplasmic cores is organized in a similar manner, indicating that the structures obtained in vitro are physiologically relevant. We discuss our results in the context of the VACV replicative cycle, and the assembly and disassembly of the infectious MV.