bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Variability of Precipitation Across Different Sectors of an Extra‐Tropical Cyclone: A Case Study Over the High‐Latitudes of the Southern Ocean
Authors: Truong S. C. H. , Siems S. T. , May P. T. , Huang Y. , Vignon É. , Gevorgyan A. 
Published: November 2023

AbstractShipborne observations from the CAPRICORN‐2018 field campaign were used to investigate the characteristics and variability of precipitation across different sectors of an extra‐tropical cyclone on 16 February 2018, over the Southern Ocean (SO). Three distinct time periods—frontal, post‐frontal, and cyclone—were identified during the day. The frontal passage recorded a total accumulation of 1.9 mm, where the precipitation phases were primarily composed of rain (96%), while the cyclone period recorded the largest precipitation (4.0 mm), where the precipitation phases varied with snow (10%), mixed‐phase (40%), and rain (50%). The BASTA radar suggests the freezing level was shallow (∼500 m) with snow present above. The cloud top heights, observed by a C‐band radar, were shallower in the cyclone period, although deeper cloud depths of ∼6 km were sporadically recorded. Increased surface fluxes and a southerly wind direction indicate that cold air advection, was likely the main cause of high precipitation during the cyclone period. A non‐precipitating multi‐layer cloud structure with a geometrically thin (200 m) homogeneous layer of supercooled liquid water (SLW) overlaying shallow boundary layer convection was seen during the post‐frontal period. The ship‐borne observations were used to evaluate Weather Research & Forecasting (WRF) simulations with different microphysics settings. We found the frontal precipitation intensity is well reproduced, but it is underestimated during the cyclone period. This study represents a unique set of observations and highlights the need for understanding how ice processes and potentially horizontal advection contribute to the development of precipitation and convection over the SO.
Modeling the Air Pollution and Aerosol‐PBL Interactions Over China Using a Variable‐Resolution Global Model
Authors: Yue Man , Dong Xinyi , Wang Minghuai , Emmons Louisa K. , Liang Yuan , Tong Dan , Liu Yawen , Liu Yaman 
Published: November 2023

AbstractModeling air quality has always been a challenge in global models constrained by coarse grids. Here, the variable‐resolution Community Atmosphere Model with full chemistry based on the scalable spectral element (SE) dynamical core (MUSICAv0) is applied in simulating air pollution with a finer grid resolution of ∼0.25° over East Asia (SE_VR), in contrast to the same model with a uniform resolution of ∼1.0° (SE_UR). Two nudging experiments and four free‐running experiments are conducted to investigate the capabilities of SE_VR in modeling the air pollution and aerosol‐planetary boundary layer (PBL) interactions over China. Results show the regional refinement in SE_VR is essential for simulating haze events over complex terrain areas attributed to its better performance in representing the local vertical and horizontal dispersion conditions. SE_VR shows prominent advantages over SE_UR in simulating surface ozone because of better resolving spatial segregation of NOx and volatile organic compounds (VOC) chemical regimes and subsequently representing more detailed chemical processes related to ozone formation, although the model generally overestimates surface ozone over China. Further analysis of SE_VR shows the daytime radiative effect of black carbon (BC) aerosols lowers PBL height by 12.0% (17.9%), and leads to an increase of PM2.5 by 14.5% (10.8%) under the moderate (severe) air pollution conditions over Sichuan Basin. However, SE_UR has deficiencies in simulating BC‐PBL interactions due to its inability to reproduce the strong inverse temperature structure caused by BC aerosols in the lower atmosphere layer. Our results highlight the value of variable‐resolution global models for simulating air pollution and its interactions with climate.
Toward an Interpretable CNN Model for the Classification of Lightning‐Produced VLF/LF Signals
Authors: Xiao Lilang , Chen Weijiang , Wang Yu , Bian Kai , Fu Zhong , Xiang Nianwen , He Hengxin , Cheng Yang 
Published: November 2023

AbstractAn interpretable convolutional neural network model is proposed for the classification of very low frequency and low frequency lightning electric field waveforms. This model adopts multi‐scale convolutional kernels and shortcut connections to enhance the ability of lightning waveform classification. Based on the data recorded from five provinces in China, the proposed model achieves an accuracy of 98.56% for a four‐type classification task including return strokes, the intra‐cloud lightning, preliminary breakdown, and narrow bipolar events. The proposed model is validated with another open‐source data set from Argentina with an accuracy of 98.45%, which shows good robustness. To ensure the classification, the features learned by the model are visualized. The class activation mapping (CAM) method is adopted to visualize the class‐specific contribution of different waveform parts by using the feature maps of the final convolutional layer. It is highlighted by the CAM method that the proposed model focuses on waveform parts that align with those areas of interests identified by human experts. The high‐contribution waveform parts are furtherly analyzed, which indicate that the proposed model possesses the capability to associate waveform features with the corresponding lightning discharge processes.
The effects of bariatric surgery on cardiac function: a systematic review and meta-analysis
Authors: Sargsyan Narek , Chen Jun Yu , Aggarwal Ravi , Fadel Michael G. , Fehervari Matyas , Ashrafian Hutan 
Published: November 2023

Abstract
Introduction
Obesity is associated with alterations in cardiac structure and haemodynamics leading to cardiovascular mortality and morbidity. Culminating evidence suggests improvement of cardiac structure and function following bariatric surgery.

Objective
To evaluate the effect of bariatric surgery on cardiac structure and function in patients before and after bariatric surgery.

Methods
Systematic review and meta-analysis of studies reporting pre- and postoperative cardiac structure and function parameters on cardiac imaging in patients undergoing bariatric surgery.

Results
Eighty studies of 3332 patients were included. Bariatric surgery is associated with a statistically significant improvement in cardiac geometry and function including a decrease of 12.2% (95% CI 0.096–0.149; p < 0.001) in left ventricular (LV) mass index, an increase of 0.155 (95% CI 0.106–0.205; p < 0.001) in E/A ratio, a decrease of 2.012 mm (95% CI 1.356–2.699; p < 0.001) in left atrial diameter, a decrease of 1.16 mm (95% CI 0.62–1.69; p < 0.001) in LV diastolic dimension, and an increase of 1.636% (95% CI 0.706–2.566; p < 0.001) in LV ejection fraction after surgery.

Conclusion
Bariatric surgery led to reverse remodelling and improvement in cardiac geometry and function driven by metabolic and haemodynamic factors.
METTL3 promotes colorectal cancer progression through activating JAK1/STAT3 signaling pathway
Authors: Sun Yuechao , Gong Weipeng , Zhang Song 
Published: November 2023

AbstractThe role of METTL3-mediated N6-methyladenosine (m6A) modification has been elucidated in several cancers, but the concrete mechanism underlying its function in colorectal cancer is still obscure. Here, we revealed that upregulated methyltransferase-like 3 (METTL3) in colorectal cancer exerted both methyltransferase activity-dependent and -independent functions in gene regulation. METTL3 deposited m6A on the 3’ untranslated region of the JAK1 transcript to promote JAK1 translation relying on YTHDF1 recognition. Besides, METTL3 was redistributed to the STAT3 promoter and worked in concert with NF-κB to facilitate STAT3 transcription, which was achieved independently on METTL3 methyltransferase activity. The increased JAK1 and STAT3 corporately contributed to the activation of the p-STAT3 signaling pathway and further upregulated downstream effectors expressions, including VEGFA and CCND1, which finally resulted in enhanced cancer cell proliferation and metastasis in vitro and in vivo. Collectively, our study revealed the unappreciated dual role of METTL3 as an m6A writer and a transcription regulator, which worked together in the same signaling pathway to drive colorectal cancer malignancy.
Mechanisms of ferroptosis and targeted therapeutic approaches in lymphoma
Authors: Yu Tiantian , Xu-Monette Zijun Y. , Yu Li , Li Yong , Young Ken H. 
Published: November 2023

AbstractLymphoma is the sixth most common type of cancer worldwide. Under the current treatment standards, patients with lymphoma often fail to respond to treatment or relapse early and require further therapy. Hence, novel therapeutic strategies need to be explored and our understanding of the molecular underpinnings of lymphomas should be expanded. Ferroptosis, a non-apoptotic regulated cell death, is characterized by increased reactive oxygen species and lipid peroxidation due to metabolic dysfunction. Excessive or lack of ferroptosis has been implicated in tumor development. Current preclinical evidences suggest that ferroptosis participates in tumorigenesis, progression, and drug resistance of lymphoma, identifying a potential biomarker and an attractive molecular target. Our review summarizes the core mechanisms and regulatory networks of ferroptosis and discusses existing evidences of ferroptosis induction for the treatment of lymphoma, with intent to provide a framework for understanding the role of ferroptosis in lymphomagenesis and a new perspective of lymphoma treatment.
Caspase-8 activation by cigarette smoke induces pro-inflammatory cell death of human macrophages exposed to lipopolysaccharide
Authors: Cristaldi Marta , Buscetta Marco , Cimino Maura , La Mensa Agnese , Giuffrè Maria Rita , Fiore Luigi , Carcione Claudia , Bucchieri Fabio , Rappa Francesca , Coronnello Claudia , Sciaraffa Nicolina , Amato Santina , Aronica Tommaso Silvano , Lo Iacono Giovanna , Bertani Alessandro , Pace Elisabetta , Cipollina Chiara 
Published: November 2023

AbstractCigarette smoking impairs the lung innate immune response making smokers more susceptible to infections and severe symptoms. Dysregulation of cell death is emerging as a key player in chronic inflammatory conditions. We have recently reported that short exposure of human monocyte-derived macrophages (hMDMs) to cigarette smoke extract (CSE) altered the TLR4-dependent response to lipopolysaccharide (LPS). CSE caused inhibition of the MyD88-dependent inflammatory response and activation of TRIF/caspase-8/caspase-1 pathway leading to Gasdermin D (GSDMD) cleavage and increased cell permeability. Herein, we tested the hypothesis that activation of caspase-8 by CSE increased pro-inflammatory cell death of LPS-stimulated macrophages. To this purpose, we measured apoptotic and pyroptotic markers as well as the expression/release of pro-inflammatory mediators in hMDMs exposed to LPS and CSE, alone or in combination, for 6 and 24 h. We show that LPS/CSE-treated hMDMs, but not cells treated with CSE or LPS alone, underwent lytic cell death (LDH release) and displayed apoptotic features (activation of caspase-8 and -3/7, nuclear condensation, and mitochondrial membrane depolarization). Moreover, the negative regulator of caspase-8, coded by CFLAR gene, was downregulated by CSE. Activation of caspase-3 led to Gasdermin E (GSDME) cleavage. Notably, lytic cell death caused the release of the damage-associated molecular patterns (DAMPs) heat shock protein-60 (HSP60) and S100A8/A9. This was accompanied by an impaired inflammatory response resulting in inhibited and delayed release of IL6 and TNF. Of note, increased cleaved caspase-3, higher levels of GSDME and altered expression of cell death-associated genes were found in alveolar macrophages of smoker subjects compared to non-smoking controls. Overall, our findings show that CSE sensitizes human macrophages to cell death by promoting pyroptotic and apoptotic pathways upon encountering LPS. We propose that while the delayed inflammatory response may result in ineffective defenses against infections, the observed cell death associated with DAMP release may contribute to establish chronic inflammation.
RMI1 facilitates repair of ionizing radiation–induced DNA damage and maintenance of genomic stability
Authors: Fang Lianying , Sun Yuxiao , Dong Mingxin , Yang Mengmeng , Hao Jianxiu , Li Jiale , Zhang Huanteng , He Ningning , Du Liqing , Xu Chang 
Published: November 2023

AbstractIonizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a crucial route responsible for repairing DSBs. RecQ-mediated genome instability protein 1 (RMI1) is a member of an evolutionarily conserved Bloom syndrome complex, which prevents and resolves aberrant recombination products during HR, thereby promoting genome stability. However, little is known about the role of RMI1 in regulating the cellular response to IR. This study aimed to understand the cellular functions and molecular mechanisms by which RMI1 maintains genomic stability after IR exposure. Here, we showed IR upregulated the RMI1 protein level and induced RMI1 relocation to the DNA damage sites. We also demonstrated that the loss of RMI1 in cells resulted in enhanced levels of DNA damage, sustained cell cycle arrest, and impaired HR repair after IR, leading to reduced cell viability and elevated genome instability. Taken together, our results highlighted the direct roles of RMI1 in response to DNA damage induced by IR and implied that RMI1 might be a new genome safeguard molecule to radiation-induced damage.
Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis
Authors: Fang Zijian , Corbizi Fattori Giuditta , McKerrell Thomas , Boucher Rebecca H. , Jackson Aimee , Fletcher Rachel S. , Forte Dorian , Martin Jose-Ezequiel , Fox Sonia , Roberts James , Glover Rachel , Harris Erica , Bridges Hannah R. , Grassi Luigi , Rodriguez-Meira Alba , Mead Adam J. , Knapper Steven , Ewing Joanne , Butt Nauman M. , Jain Manish , Francis Sebastian , Clark Fiona J. , Coppell Jason , McMullin Mary F. , Wadelin Frances , Narayanan Srinivasan , Milojkovic Dragana , Drummond Mark W. , Sekhar Mallika , ElDaly Hesham , Hirst Judy , Paramor Maike , Baxter E. Joanna , Godfrey Anna L. , Harrison Claire N. , Méndez-Ferrer Simón 
Published: November 2023

AbstractCurrent therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen’s safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2V617F, CALRins5 or CALRdel52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study’s A’herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk.
The rate of epigenetic drift scales with maximum lifespan across mammals
Authors: Bertucci-Richter Emily M. , Parrott Benjamin B. 
Published: November 2023

AbstractEpigenetic drift or “disorder” increases across the mouse lifespan and is suggested to underlie epigenetic clock signals. While the role of epigenetic drift in determining maximum lifespan across species has been debated, robust tests of this hypothesis are lacking. Here, we test if epigenetic disorder at various levels of genomic resolution explains maximum lifespan across four mammal species. We show that epigenetic disorder increases with age in all species and at all levels of genomic resolution tested. The rate of disorder accumulation occurs faster in shorter lived species and corresponds to species adjusted maximum lifespan. While the density of cytosine-phosphate-guanine dinucleotides (“CpGs”) is negatively associated with the rate of age-associated disorder accumulation, it does not fully explain differences across species. Our findings support the hypothesis that the rate of epigenetic drift explains maximum lifespan and provide partial support for the hypothesis that CpG density buffers against epigenetic drift.
Gene duplication and deletion caused by over-replication at a fork barrier
Authors: Oehler Judith , Morrow Carl A. , Whitby Matthew C. 
Published: November 2023

AbstractReplication fork stalling can provoke fork reversal to form a four-way DNA junction. This remodelling of the replication fork can facilitate repair, aid bypass of DNA lesions, and enable replication restart, but may also pose a risk of over-replication during fork convergence. We show that replication fork stalling at a site-specific barrier in fission yeast can induce gene duplication-deletion rearrangements that are independent of replication restart-associated template switching and Rad51-dependent multi-invasion. Instead, they resemble targeted gene replacements (TGRs), requiring the DNA annealing activity of Rad52, the 3’-flap nuclease Rad16-Swi10, and mismatch repair protein Msh2. We propose that excess DNA, generated during the merging of a canonical fork with a reversed fork, can be liberated by a nuclease and integrated at an ectopic site via a TGR-like mechanism. This highlights how over-replication at replication termination sites can threaten genome stability in eukaryotes.
Diversity of cortical activity changes beyond depression during Spreading Depolarizations
Authors: Nasretdinov Azat , Vinokurova Daria , Lemale Coline L. , Burkhanova-Zakirova Gulshat , Chernova Ksenia , Makarova Julia , Herreras Oscar , Dreier Jens P. , Khazipov Roustem 
Published: November 2023

AbstractSpreading depolarizations (SDs) are classically thought to be associated with spreading depression of cortical activity. Here, we found that SDs in patients with subarachnoid hemorrhage produce variable, ranging from depression to booming, changes in electrocorticographic activity, especially in the delta frequency band. In rats, depression of activity was characteristic of high-potassium-induced full SDs, whereas partial superficial SDs caused either little change or a boom of activity at the cortical vertex, supported by volume conduction of signals from spared delta generators in the deep cortical layers. Partial SDs also caused moderate neuronal depolarization and sustained excitation, organized in gamma oscillations in a narrow sub-SD zone. Thus, our study challenges the concept of homology between spreading depolarization and spreading depression by showing that SDs produce variable, from depression to booming, changes in activity at the cortical surface and in different cortical layers depending on the depth of SD penetration.
Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance
Authors: Diniz Fabiola , Ngo Nguyen Yen Nhi , Colon-Leyva Mariel , Edgington-Giordano Francesca , Hilliard Sylvia , Zwezdaryk Kevin , Liu Jiao , El-Dahr Samir S. , Tortelote Giovane G. 
Published: November 2023

AbstractNephron endowment at birth impacts long-term renal and cardiovascular health, and it is contingent on the nephron progenitor cell (NPC) pool. Glycolysis modulation is essential for determining NPC fate, but the underlying mechanism is unclear. Combining RNA sequencing and quantitative proteomics we identify 267 genes commonly targeted by Wnt activation or glycolysis inhibition in NPCs. Several of the impacted pathways converge at Acetyl-CoA, a co-product of glucose metabolism. Notably, glycolysis inhibition downregulates key genes of the Mevalonate/cholesterol pathway and stimulates NPC differentiation. Sodium acetate supplementation rescues glycolysis inhibition effects and favors NPC maintenance without hindering nephrogenesis. Six2Cre-mediated removal of ATP-citrate lyase (Acly), an enzyme that converts citrate to acetyl-CoA, leads to NPC pool depletion, glomeruli count reduction, and increases Wnt4 expression at birth. Sodium acetate supplementation counters the effects of Acly deletion on cap-mesenchyme. Our findings show a pivotal role of acetyl-CoA metabolism in kidney development and uncover new avenues for manipulating nephrogenesis and preventing adult kidney disease.
Cryogenic multiplexing using selective area grown nanowires
Authors: Olšteins Dāgs , Nagda Gunjan , Carrad Damon J. , Beznasyuk Daria V. , Petersen Christian E. N. , Martí-Sánchez Sara , Arbiol Jordi , Jespersen Thomas S. 
Published: November 2023

AbstractBottom-up grown nanomaterials play an integral role in the development of quantum technologies but are often challenging to characterise on large scales. Here, we harness selective area growth of semiconductor nanowires to demonstrate large-scale integrated circuits and characterisation of large numbers of quantum devices. The circuit consisted of 512 quantum devices embedded within multiplexer/demultiplexer pairs, incorporating thousands of interconnected selective area growth nanowires operating under deep cryogenic conditions. Multiplexers enable a range of new strategies in quantum device research and scaling by increasing the device count while limiting the number of connections between room-temperature control electronics and the cryogenic samples. As an example of this potential we perform a statistical characterization of large arrays of identical quantum dots thus establishing the feasibility of applying cross-bar gating strategies for efficient scaling of future selective area growth quantum circuits. More broadly, the ability to systematically characterise large numbers of devices provides new levels of statistical certainty to materials/device development.
Modulation of insulin secretion by RBFOX2-mediated alternative splicing
Authors: Moss Nicole D. , Wells Kristen L. , Theis Alexandra , Kim Yong-Kyung , Spigelman Aliya F. , Liu Xiong , MacDonald Patrick E. , Sussel Lori 
Published: November 2023

AbstractInsulin secretion is a tightly regulated process that is vital for maintaining blood glucose homeostasis. Although the molecular components of insulin granule trafficking and secretion are well established, how they are regulated to rapidly fine-tune secretion in response to changing environmental conditions is not well characterized. Recent studies have determined that dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing occurs at the onset of diabetes. We demonstrate that the RBP, RBFOX2, is a critical regulator of insulin secretion through the alternative splicing of genes required for insulin granule docking and exocytosis. Conditional mutation of Rbfox2 in the mouse pancreas results in decreased insulin secretion and impaired blood glucose homeostasis. Consistent with defects in secretion, we observe reduced insulin granule docking and corresponding splicing defects in the SNARE complex components. These findings identify an additional mechanism for modulating insulin secretion in both healthy and dysfunctional pancreatic β cells.