bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adeno-associated virus delivered CXCL9 sensitizes glioblastoma to anti-PD-1 immune checkpoint blockade
Authors: von Roemeling Christina A. , Patel Jeet A. , Carpenter Savannah L. , Yegorov Oleg , Yang Changlin , Bhatia Alisha , Doonan Bently P. , Russell Rylynn , Trivedi Vrunda S. , Klippel Kelena , Ryu Daniel H. , Grippin Adam , Futch Hunter S. , Ran Yong , Hoang-Minh Lan B. , Weidert Frances L. , Golde Todd E. , Mitchell Duane A. 
Published: July 2024

AbstractThere are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic combinatorial treatments to achieve appreciable therapeutic effects. However, developing combination therapies is difficult due to dose-limiting toxicities, blood-brain-barrier, and suppressive tumor microenvironment. Glioblastoma is notoriously devoid of lymphocytes driven in part by a paucity of lymphocyte trafficking factors necessary to prompt their recruitment and activation. Herein, we develop a recombinant adeno-associated virus (AAV) gene therapy that enables focal and stable reconstitution of the tumor microenvironment with C-X-C motif ligand 9 (CXCL9), a powerful call-and-receive chemokine for lymphocytes. By manipulating local chemokine directional guidance, AAV-CXCL9 increases tumor infiltration by cytotoxic lymphocytes, sensitizing glioblastoma to anti-PD-1 immune checkpoint blockade in female preclinical tumor models. These effects are accompanied by immunologic signatures evocative of an inflamed tumor microenvironment. These findings support AAV gene therapy as an adjuvant for reconditioning glioblastoma immunogenicity given its safety profile, tropism, modularity, and off-the-shelf capability.
Glucose-6-phosphate dehydrogenase maintains redox homeostasis and biosynthesis in LKB1-deficient KRAS-driven lung cancer
Authors: Lan Taijin , Arastu Sara , Lam Jarrick , Kim Hyungsin , Wang Wenping , Wang Samuel , Bhatt Vrushank , Lopes Eduardo Cararo , Hu Zhixian , Sun Michael , Luo Xuefei , Ghergurovich Jonathan M. , Su Xiaoyang , Rabinowitz Joshua D. , White Eileen , Guo Jessie Yanxiang 
Published: July 2024

AbstractCancer cells depend on nicotinamide adenine dinucleotide phosphate (NADPH) to combat oxidative stress and support reductive biosynthesis. One major NADPH production route is the oxidative pentose phosphate pathway (committed step: glucose-6-phosphate dehydrogenase, G6PD). Alternatives exist and can compensate in some tumors. Here, using genetically-engineered lung cancer mouse models, we show that G6PD ablation significantly suppresses KrasG12D/+;Lkb1-/- (KL) but not KrasG12D/+;P53-/- (KP) lung tumorigenesis. In vivo isotope tracing and metabolomics reveal that G6PD ablation significantly impairs NADPH generation, redox balance, and de novo lipogenesis in KL but not KP lung tumors. Mechanistically, in KL tumors, G6PD ablation activates p53, suppressing tumor growth. As tumors progress, G6PD-deficient KL tumors increase an alternative NADPH source from serine-driven one carbon metabolism, rendering associated tumor-derived cell lines sensitive to serine/glycine depletion. Thus, oncogenic driver mutations determine lung cancer dependence on G6PD, whose targeting is a potential therapeutic strategy for tumors harboring KRAS and LKB1 co-mutations.
Arabidopsis and maize terminator strength is determined by GC content, polyadenylation motifs and cleavage probability
Authors: Gorjifard Sayeh , Jores Tobias , Tonnies Jackson , Mueth Nicholas A. , Bubb Kerry , Wrightsman Travis , Buckler Edward S. , Fields Stanley , Cuperus Josh T. , Queitsch Christine 
Published: July 2024

AbstractThe 3’ end of a gene, often called a terminator, modulates mRNA stability, localization, translation, and polyadenylation. Here, we adapted Plant STARR-seq, a massively parallel reporter assay, to measure the activity of over 50,000 terminators from the plants Arabidopsis thaliana and Zea mays. We characterize thousands of plant terminators, including many that outperform bacterial terminators commonly used in plants. Terminator activity is species-specific, differing in tobacco leaf and maize protoplast assays. While recapitulating known biology, our results reveal the relative contributions of polyadenylation motifs to terminator strength. We built a computational model to predict terminator strength and used it to conduct in silico evolution that generated optimized synthetic terminators. Additionally, we discover alternative polyadenylation sites across tens of thousands of terminators; however, the strongest terminators tend to have a dominant cleavage site. Our results establish features of plant terminator function and identify strong naturally occurring and synthetic terminators.
Nitrifying niche in estuaries is expanded by the plastisphere
Authors: Su Xiaoxuan , Huang Xinrong , Zhang Yiyue , Yang Leyang , Wen Teng , Yang Xiaoru , Zhu Guibing , Zhang Jinbo , Tang Yijia , Li Zhaolei , Ding Jing , Li Ruilong , Pan Junliang , Chen Xinping , Huang Fuyi , Rillig Matthias C. , Zhu Yong-guan 
Published: July 2024

AbstractThe estuarine plastisphere, a novel ecological habitat in the Anthropocene, has garnered global concerns. Recent geochemical evidence has pointed out its potential role in influencing nitrogen biogeochemistry. However, the biogeochemical significance of the plastisphere and its mechanisms regulating nitrogen cycling remain elusive. Using 15N- and 13C-labelling coupled with metagenomics and metatranscriptomics, here we unveil that the plastisphere likely acts as an underappreciated nitrifying niche in estuarine ecosystems, exhibiting a 0.9 ~ 12-fold higher activity of bacteria-mediated nitrification compared to surrounding seawater and other biofilms (stone, wood and glass biofilms). The shift of active nitrifiers from O2-sensitive nitrifiers in the seawater to nitrifiers with versatile metabolisms in the plastisphere, combined with the potential interspecific cooperation of nitrifying substrate exchange observed among the plastisphere nitrifiers, collectively results in the unique nitrifying niche. Our findings highlight the plastisphere as an emerging nitrifying niche in estuarine environment, and deepen the mechanistic understanding of its contribution to marine biogeochemistry.
Stress-induced nuclear translocation of ONAC023 improves drought and heat tolerance through multiple processes in rice
Authors: Chang Yu , Fang Yujie , Liu Jiahan , Ye Tiantian , Li Xiaokai , Tu Haifu , Ye Ying , Wang Yao , Xiong Lizhong 
Published: July 2024

AbstractDrought and heat are major abiotic stresses frequently coinciding to threaten rice production. Despite hundreds of stress-related genes being identified, only a few have been confirmed to confer resistance to multiple stresses in crops. Here we report ONAC023, a hub stress regulator that integrates the regulations of both drought and heat tolerance in rice. ONAC023 positively regulates drought and heat tolerance at both seedling and reproductive stages. Notably, the functioning of ONAC023 is obliterated without stress treatment and can be triggered by drought and heat stresses at two layers. The expression of ONAC023 is induced in response to stress stimuli. We show that overexpressed ONAC23 is translocated to the nucleus under stress and evidence from protoplasts suggests that the dephosphorylation of the remorin protein OSREM1.5 can promote this translocation. Under drought or heat stress, the nuclear ONAC023 can target and promote the expression of diverse genes, such as OsPIP2;7, PGL3, OsFKBP20-1b, and OsSF3B1, which are involved in various processes including water transport, reactive oxygen species homeostasis, and alternative splicing. These results manifest that ONAC023 is fine-tuned to positively regulate drought and heat tolerance through the integration of multiple stress-responsive processes. Our findings provide not only an underlying connection between drought and heat responses, but also a promising candidate for engineering multi-stress-resilient rice.
Sensor degradation in nuclear reactor pressure vessels: the overlooked factor in remaining useful life prediction
Authors: Hossain Raisa Bentay , Kobayashi Kazuma , Alam Syed Bahauddin 
Published: July 2024

AbstractSensor degradation poses a critical yet ‘often overlooked’ challenge in accurately predicting the remaining useful life (RUL) of nuclear reactor pressure vessels (RPVs), hindering safe and efficient plant operation. This paper introduces an approach to RUL estimation that explicitly addresses sensor degradation, a significant departure from conventional methods. We model neutron embrittlement, a dominant degradation process in RPV steel, as a Wiener process and leverage real-world surveillance capsule data for insightful parameterization. Maximum likelihood estimation is utilized to characterize the degradation dynamics in the model. A Kalman filter then seamlessly integrates the degradation model with sensor measurements, effectively compensating for degradation-induced errors and providing refined state estimates. These estimates power a robust RUL prediction framework. Our results expose the profound impact of sensor degradation on conventional RUL predictions. By directly confronting sensor degradation, our method yields substantially more accurate and reliable RUL estimates. This work marks a significant advancement in the field of materials degradation, offering a powerful tool to optimize nuclear power plant safety and longevity.
Priming antibody responses to the fusion peptide in rhesus macaques
Authors: Cottrell Christopher A. , Pratap Payal P. , Cirelli Kimberly M. , Carnathan Diane G. , Enemuo Chiamaka A. , Antanasijevic Aleksandar , Ozorowski Gabriel , Sewall Leigh M. , Gao Hongmei , Allen Joel D. , Nogal Bartek , Silva Murillo , Bhiman Jinal , Pauthner Matthias , Irvine Darrell J. , Montefiori David , Crispin Max , Burton Dennis R. , Silvestri Guido , Crotty Shane , Ward Andrew B. 
Published: July 2024

AbstractImmunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.
Neutrophil-derived migrasomes are an essential part of the coagulation system
Authors: Jiang Dong , Jiao Lin , Li Qing , Xie Renxiang , Jia Haohao , Wang ShiHui , Chen Yining , Liu Siyuan , Huang Dandan , Zheng Jiajia , Song Wenhao , Li Ying , Chen JianFeng , Li Jinsong , Ying Binwu , Yu Li 
Published: July 2024

AbstractMigrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.
Emergence of lake conditions that exceed natural temperature variability
Authors: Huang Lei , Woolway R. Iestyn , Timmermann Axel , Lee Sun-Seon , Rodgers Keith B. , Yamaguchi Ryohei 
Published: July 2024

AbstractLake surface temperatures are projected to increase under climate change, which could trigger shifts in the future distribution of thermally sensitive aquatic species. Of particular concern for lake ecosystems are when temperatures increase outside the range of natural variability, without analogue either today or in the past. However, our knowledge of when such no-analogue conditions will appear remains uncertain. Here, using daily outputs from a large ensemble of SSP3-7.0 Earth system model projections, we show that these conditions will emerge at the surface of many northern lakes under a global warming of 4.0 °C above pre-industrial conditions. No-analogue conditions will occur sooner, under 2.4 °C of warming, at lower latitudes, primarily due to a weaker range of natural variability, which increases the likelihood of the upper natural limit of lake temperature being exceeded. Similar patterns are also projected in subsurface water, with no-analogue conditions occurring first at low latitudes and occurring last, if at all, at higher latitudes. Our study suggests that global warming will induce changes across the water column, particularly at low latitudes, leading to the emergence of unparalleled climates with no modern counterparts, probably affecting their habitability and leading to rearrangements of freshwater habitats this century.
Precise in vivo RNA base editing with a wobble-enhanced circular CLUSTER guide RNA
Authors: Reautschnig Philipp , Fruhner Carolin , Wahn Nicolai , Wiegand Charlotte P. , Kragness Sabrina , Yung John F. , Hofacker Daniel T. , Fisk Jenna , Eidelman Michelle , Waffenschmidt Nils , Feige Maximilian , Pfeiffer Laura S. , Schulz Annika E. , Füll Yvonne , Levanon Erez Y. , Mandel Gail , Stafforst Thorsten 
Published: July 2024

AbstractRecruiting the endogenous editing enzyme adenosine deaminase acting on RNA (ADAR) with tailored guide RNAs for adenosine-to-inosine (A-to-I) RNA base editing is promising for safely manipulating genetic information at the RNA level. However, the precision and efficiency of editing are often compromised by bystander off-target editing. Here, we find that in 5′-UAN triplets, which dominate bystander editing, G•U wobble base pairs effectively mitigate off-target events while maintaining high on-target efficiency. This strategy is universally applicable to existing A-to-I RNA base-editing systems and complements other suppression methods such as G•A mismatches and uridine (U) depletion. Combining wobble base pairing with a circularized format of the CLUSTER approach achieves highly precise and efficient editing (up to 87%) of a disease-relevant mutation in the Mecp2 transcript in cell culture. Virus-mediated delivery of the guide RNA alone realizes functional MeCP2 protein restoration in the central nervous system of a murine Rett syndrome model with editing yields of up to 19% and excellent bystander control in vivo.
Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder
Authors: Provenza Nicole R. , Reddy Sandesh , Allam Anthony K. , Rajesh Sameer V. , Diab Nabeel , Reyes Gabriel , Caston Rose M. , Katlowitz Kalman A. , Gandhi Ajay D. , Bechtold Raphael A. , Dang Huy Q. , Najera Ricardo A. , Giridharan Nisha , Kabotyanski Katherine E. , Momin Faiza , Hasen Mohammed , Banks Garrett P. , Mickey Brian J. , Kious Brent M. , Shofty Ben , Hayden Benjamin Y. , Herron Jeffrey A. , Storch Eric A. , Patel Ankit B. , Goodman Wayne K. , Sheth Sameer A. 
Published: July 2024

AbstractRecent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy (NCT05915741). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.
Case study on climate change effects and food security in Southeast Asia
Authors: Taniushkina Daria , Lukashevich Aleksander , Shevchenko Valeriy , Belalov Ilya S. , Sotiriadi Nazar , Narozhnaia Veronica , Kovalev Kirill , Krenke Alexander , Lazarichev Nikita , Bulkin Alexander , Maximov Yury 
Published: July 2024

AbstractAgriculture, a cornerstone of human civilization, faces rising challenges from climate change, resource limitations, and stagnating yields. Precise crop production forecasts are crucial for shaping trade policies, development strategies, and humanitarian initiatives. This study introduces a comprehensive machine learning framework designed to predict crop production. We leverage CMIP5 climate projections under a moderate carbon emission scenario to evaluate the future suitability of agricultural lands and incorporate climatic data, historical agricultural trends, and fertilizer usage to project yield changes. Our integrated approach forecasts significant regional variations in crop production across Southeast Asia by 2028, identifying potential cropland utilization. Specifically, the cropland area in Indonesia, Malaysia, Philippines, and Viet Nam is projected to decline by more than 10% if no action is taken, and there is potential to mitigate that loss. Moreover, rice production is projected to decline by 19% in Viet Nam and 7% in Thailand, while the Philippines may see a 5% increase compared to 2021 levels. Our findings underscore the critical impacts of climate change and human activities on agricultural productivity, offering essential insights for policy-making and fostering international cooperation.
Multiparametric MRI–based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer
Authors: Mohamed Rania M. , Panthi Bikash , Adrada Beatriz E. , Boge Medine , Candelaria Rosalind P. , Chen Huiqin , Guirguis Mary S. , Hunt Kelly K. , Huo Lei , Hwang Ken-Pin , Korkut Anil , Litton Jennifer K. , Moseley Tanya W. , Pashapoor Sanaz , Patel Miral M. , Reed Brandy , Scoggins Marion E. , Son Jong Bum , Thompson Alastair , Tripathy Debu , Valero Vicente , Wei Peng , White Jason , Whitman Gary J. , Xu Zhan , Yang Wei , Yam Clinton , Ma Jingfei , Rauch Gaiane M. 
Published: July 2024

AbstractTriple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.
Optimizing word embeddings for small datasets: a case study on patient portal messages from breast cancer patients
Authors: Song Qingyuan , Ni Congning , Warner Jeremy L. , Chen Qingxia , Song Lijun , Rosenbloom S. Trent , Malin Bradley A. , Yin Zhijun 
Published: July 2024

AbstractPatient portal messages often relate to specific clinical phenomena (e.g., patients undergoing treatment for breast cancer) and, as a result, have received increasing attention in biomedical research. These messages require natural language processing and, while word embedding models, such as word2vec, have the potential to extract meaningful signals from text, they are not readily applicable to patient portal messages. This is because embedding models typically require millions of training samples to sufficiently represent semantics, while the volume of patient portal messages associated with a particular clinical phenomenon is often relatively small. We introduce a novel adaptation of the word2vec model, PK-word2vec (where PK stands for prior knowledge), for small-scale messages. PK-word2vec incorporates the most similar terms for medical words (including problems, treatments, and tests) and non-medical words from two pre-trained embedding models as prior knowledge to improve the training process. We applied PK-word2vec in a case study of patient portal messages in the Vanderbilt University Medical Center electric health record system sent by patients diagnosed with breast cancer from December 2004 to November 2017. We evaluated the model through a set of 1000 tasks, each of which compared the relevance of a given word to a group of the five most similar words generated by PK-word2vec and a group of the five most similar words generated by the standard word2vec model. We recruited 200 Amazon Mechanical Turk (AMT) workers and 7 medical students to perform the tasks. The dataset was composed of 1389 patient records and included 137,554 messages with 10,683 unique words. Prior knowledge was available for 7981 non-medical and 1116 medical words. In over 90% of the tasks, both reviewers indicated PK-word2vec generated more similar words than standard word2vec (p = 0.01).The difference in the evaluation by AMT workers versus medical students was negligible for all comparisons of tasks’ choices between the two groups of reviewers ($${\text{p}} = 0.774$$

p
=
0.774

under a paired t-test). PK-word2vec can effectively learn word representations from a small message corpus, marking a significant advancement in processing patient portal messages.