bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMIP Simulations of a Global Model for Unified Weather‐Climate Forecast: Understanding Precipitation Characteristics and Sensitivity Over East Asia
Authors: Zhang Yi , Yu Rucong , Li Jian , Li Xiaohan , Rong Xinyao , Peng Xindong , Zhou Yihui 
Published: November 2021

AbstractA global model formulation for unified weather‐climate forecast is evaluated, with emphasis on the climate simulations at typical hydrostatic resolutions. The internal sensitivity is explored by considering different dynamical configurations (resolution, solver type, transport scheme). After a basic assessment of the global mean climate, a detailed analysis of precipitation characteristics is extended to East Asia. The model shows a reasonable mean state, seasonal variation, frequency–intensity structure, and diurnal phase time. The artificial rainfall around the steep slopes of the Tibetan Plateau can be improved through choices in the dynamical configuration. The regional features characterized by “afternoon versus nocturnal‐to‐early‐morning peaks” are properly distinguished. The hourly climatic features are comparable to super‐parameterized CAM5. Different dynamical configurations demonstrate unique sensitivities related to underling physical mechanisms, which are studied from the perspective of the diurnal cycle for three representative regions. Over South China, the higher‐resolution models decrease the weak‐precipitation while increase intense rainfall, thus reducing the dry biases. This is contributed by enhanced grid and sub‐grid scale motions associated with daytime convection progression. Over central western China, the variable‐resolution model better simulates the eastward propagating episodes characterized by a transition from convective to stratiform rainfall along the eastern slope of the Plateau. This reduces the positive biases at the high topography of the Plateau and alleviates the negative biases at the lower foot. Over central eastern China, the model replicates the dominant role of large‐scale governing factors in regulating the early morning rainfall peaks, and produces stratiform heating patterns.
Influences of Extreme Events on Water and Carbon Cycles of Cropland Ecosystems: A Comprehensive Exploration Combining Site and Global Modeling
Authors: Xia Ye , Fu Congsheng , Wu Haohao , Wu Huawu , Zhang Haixia , Cao Yang , Zhu Zichun 
Published: November 2021

AbstractClimate warming increases the frequencies of drought and excessive precipitation, and the influencing mechanisms and magnitudes of these extreme events on the water and carbon cycles of different crops still remain unclear. In this study, single‐point simulations for six irrigated and rain‐fed crops and global simulation were combined to comprehensively investigate the impacts of drought and excessive precipitation on evapotranspiration (ET), irrigation, net ecosystem exchange (NEE), and yields of crops. Results illustrated that the AgroIBIS‐based CLM5 simulated ET and NEE dynamics well for rice, corn, winter wheat, soybeans, sugar beets, and potatoes after parameter optimization. The impacts of abnormal precipitation on ET, NEE, and crop yield were larger at rain‐fed sites than at irrigated sites. The influencing magnitudes of precipitation shortage on ET depended on the occurring time of drought events relative to the growth stages of crops. Precipitation shortage (excessive precipitation) reduced (increased) ET and net carbon uptake by 4%–19% (4%–7%) and 3%–15% (1%–6%) compared to normal precipitation years at irrigated sites, while corresponding decrease (increase) was 7%–35% (24%–27%) and 19%–48% (12%–34%) at rain‐fed sites. The proportional influencing magnitudes of precipitation shortage on ET, NEE, and yield increased sequentially for rain‐fed crops. At the global scale, the simulated theoretical irrigation in extremely dry years was 25%–75% larger than that in normal precipitation years, and the actual irrigation was 3.5–4.0 times as large as the simulated theoretical value at irrigated sites, implying that drought intensified water resource shortage through excessive irrigation besides precipitation shortage.
Do presenting symptoms, use of pre-diagnostic endoscopy and risk of emergency cancer diagnosis vary by comorbidity burden and type in patients with colorectal cancer?
Authors: Majano Sara Benitez , Lyratzopoulos Georgios , Rachet Bernard , de Wit Niek J. , Renzi Cristina 
Published: November 2021

Abstract
Background
Cancer patients often have pre-existing comorbidities, which can influence timeliness of cancer diagnosis. We examined symptoms, investigations and emergency presentation (EP) risk among colorectal cancer (CRC) patients by comorbidity status.

Methods
Using linked cancer registration, primary care and hospital records of 4836 CRC patients (2011–2015), and multivariate quantile and logistic regression, we examined variations in specialist investigations, diagnostic intervals and EP risk.

Results
Among colon cancer patients, 46% had at least one pre-existing hospital-recorded comorbidity, most frequently cardiovascular disease (CVD, 18%). Comorbid versus non-comorbid cancer patients more frequently had records of anaemia (43% vs 38%), less frequently rectal bleeding/change in bowel habit (20% vs 27%), and longer intervals from symptom-to-first relevant test (median 136 vs 74 days). Comorbid patients were less likely investigated with colonoscopy/sigmoidoscopy, independently of symptoms (adjusted OR = 0.7[0.6, 0.9] for Charlson comorbidity score 1–2 and OR = 0.5 [0.4–0.7] for score 3+ versus 0. EP risk increased with comorbidity score 0, 1, 2, 3+: 23%, 35%, 33%, 47%; adjusted OR = 1.8 [1.4, 2.2]; 1.7 [1.3, 2.3]; 3.0 [2.3, 4.0]) and for patients with CVD (adjusted OR = 2.0 [1.5, 2.5]).

Conclusions
Comorbid individuals with as-yet-undiagnosed CRC often present with general rather than localising symptoms and are less likely promptly investigated with colonoscopy/sigmoidoscopy. Comorbidity is a risk factor for diagnostic delay and has potential, additionally to symptoms, as risk-stratifier for prioritising patients needing prompt assessment to reduce EP.
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1
Authors: Pan Jinghua , Qiao Yiting , Chen Congcong , Zang Hongjing , Zhang Xiaojing , Qi Feng , Chang Cunjie , Yang Fan , Sun Mengqing , Lin Shengbin , Tang Quandong , Li Lina , Wang Menglan , Wu Minjie , Liu Yongzhu , Lai Caiyong , Chen Jianxiang , Chen Guo 
Published: November 2021

AbstractPD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.
Comparison of culture, confocal microscopy and PCR in routine hospital use for microbial keratitis diagnosis
Authors: Hoffman Jeremy J. , Dart John K. G. , De Surjo K. , Carnt Nicole , Cleary Georgia , Hau Scott 
Published: November 2021

Abstract
Aims
To evaluate the sensitivity and specificity of polymerase chain reaction (PCR), in vivo confocal microscopy (IVCM) and culture for microbial keratitis (MK) diagnosis.

Methods
Retrospective review of PCR, IVCM and culture results for MK diagnosis at Moorfields Eye Hospital between August 2013 and December 2014.

Results
PCR results were available for 259 MK patients with concurrent culture for 203/259 and IVCM for 149/259. Sensitivities and specificities with 95% confidence intervals [95% CI] were calculated for Acanthamoeba keratitis (AK) and fungal keratitis (FK), by comparison with culture, for both IVCM and PCR. For AK, FK and bacterial keratitis (BK) sensitivities were calculated, for each diagnostic method, by comparison with a composite reference standard (a positive result for one or more of culture, PCR or IVCM having a specificity of 100% by definition). For the latter, sensitivities with [95% CI] were: for AK, IVCM 77.1% [62.7–88.0%], PCR 63.3% [48.3–76.6%], culture 35.6 [21.9–51.2]; for FK, IVCM 81.8% [48.2–97.7%], PCR 30.8% [9.09–61.4%], culture 41.7% [15.2–72.3%]; for BK, PCR 25.0% [14.7–37.9%], culture 95.6% [87.6–99.1%].

Conclusion
IVCM was the most sensitive technique for AK and FK diagnosis but culture remains our gold standard for BK. These findings reflect results to be expected from service providers to UK ophthalmology units and demonstrates the need at our centre for ongoing diagnostic result audit leading to the potential to improve PCR diagnosis. Both FK and AK are now common in the UK; ophthalmology units need to have all these techniques available to optimise their MK management.
Middle Ordovician astrochronology decouples asteroid breakup from glacially-induced biotic radiations
Authors: Rasmussen Jan Audun , Thibault Nicolas , Mac Ørum Rasmussen Christian 
Published: November 2021

AbstractMeso-Cenozoic evidence suggests links between changes in the expression of orbital changes and millennia-scale climatic- and biotic variations, but proof for such shifts in orbital cyclicity farther back in geological time is lacking. Here, we report a 469-million-year-old Palaeozoic energy transfer from precession to 405 kyr eccentricity cycles that coincides with the start of the Great Ordovician Biodiversification Event (GOBE). Based on an early Middle Ordovician astronomically calibrated cyclostratigraphic framework we find this orbital change to succeed the onset of icehouse conditions by 200,000 years, suggesting a climatic origin. Recently, this icehouse was postulated to be facilitated by extra-terrestrial dust associated with an asteroid breakup. Our timescale, however, shows the meteor bombardment to post-date the icehouse by 800,000 years, instead pausing the GOBE 600,000 years after its initiation. Resolving Milankovitch cyclicity in deep time thus suggests universal orbital control in modulating climate, and maybe even biodiversity accumulation, through geological time.
Rare t(X;14)(q28;q32) translocation reveals link between MTCP1 and chronic lymphocytic leukemia
Authors: Walker Janek S. , Hing Zachary A. , Sher Steven , Cronin James , Williams Katie , Harrington Bonnie , Skinner Jordan N. , Cempre Casey B. , Gregory Charles T. , Pan Alexander , Yano Max , Beaver Larry P. , Walker Brandi R. , Labanowska Jadwiga M. , Heerema Nyla A. , Mrózek Krzysztof , Woyach Jennifer A. , Ruppert Amy S. , Lehman Amy , Ozer Hatice Gulcin , Coppola Vincenzo , Yan Pearlly , Byrd John C. , Blachly James S. , Lapalombella Rosa 
Published: November 2021

AbstractRare, recurrent balanced translocations occur in a variety of cancers but are often not functionally interrogated. Balanced translocations with the immunoglobulin heavy chain locus (IGH; 14q32) in chronic lymphocytic leukemia (CLL) are infrequent but have led to the discovery of pathogenic genes including CCND1, BCL2, and BCL3. Following identification of a t(X;14)(q28;q32) translocation that placed the mature T cell proliferation 1 gene (MTCP1) adjacent to the immunoglobulin locus in a CLL patient, we hypothesized that this gene may have previously unrecognized importance. Indeed, here we report overexpression of human MTCP1 restricted to the B cell compartment in mice produces a clonal CD5+/CD19+ leukemia recapitulating the major characteristics of human CLL and demonstrates favorable response to therapeutic intervention with ibrutinib. We reinforce the importance of genetic interrogation of rare, recurrent balanced translocations to identify cancer driving genes via the story of MTCP1 as a contributor to CLL pathogenesis.
Computational design and optimization of electro-physiological sensors
Authors: Nittala Aditya Shekhar , Karrenbauer Andreas , Khan Arshad , Kraus Tobias , Steimle Jürgen 
Published: November 2021

AbstractElectro-physiological sensing devices are becoming increasingly common in diverse applications. However, designing such sensors in compact form factors and for high-quality signal acquisition is a challenging task even for experts, is typically done using heuristics, and requires extensive training. Our work proposes a computational approach for designing multi-modal electro-physiological sensors. By employing an optimization-based approach alongside an integrated predictive model for multiple modalities, compact sensors can be created which offer an optimal trade-off between high signal quality and small device size. The task is assisted by a graphical tool that allows to easily specify design preferences and to visually analyze the generated designs in real-time, enabling designer-in-the-loop optimization. Experimental results show high quantitative agreement between the prediction of the optimizer and experimentally collected physiological data. They demonstrate that generated designs can achieve an optimal balance between the size of the sensor and its signal acquisition capability, outperforming expert generated solutions.
Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes
Authors: Jindal Sonali , Pennock Nathan D. , Sun Duanchen , Horton Wesley , Ozaki Michelle K. , Narasimhan Jayasri , Bartlett Alexandra Q. , Weinmann Sheila , Goss Paul E. , Borges Virginia F. , Xia Zheng , Schedin Pepper 
Published: November 2021

AbstractYoung women’s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.
A habenula-insular circuit encodes the willingness to act
Authors: Khalighinejad Nima , Garrett Neil , Priestley Luke , Lockwood Patricia , Rushworth Matthew F. S. 
Published: November 2021

AbstractThe decision that it is worth doing something rather than nothing is a core yet understudied feature of voluntary behaviour. Here we study “willingness to act”, the probability of making a response given the context. Human volunteers encountered opportunities to make effortful actions in order to receive rewards, while watching a movie inside a 7 T MRI scanner. Reward and other context features determined willingness-to-act. Activity in the habenula tracked trial-by-trial variation in participants’ willingness-to-act. The anterior insula encoded individual environment features that determined this willingness. We identify a multi-layered network in which contextual information is encoded in the anterior insula, converges on the habenula, and is then transmitted to the supplementary motor area, where the decision is made to either act or refrain from acting via the nigrostriatal pathway.
Physics-informed deep learning characterizes morphodynamics of Asian soybean rust disease
Authors: Cavanagh Henry , Mosbach Andreas , Scalliet Gabriel , Lind Rob , Endres Robert G. 
Published: November 2021

AbstractMedicines and agricultural biocides are often discovered using large phenotypic screens across hundreds of compounds, where visible effects of whole organisms are compared to gauge efficacy and possible modes of action. However, such analysis is often limited to human-defined and static features. Here, we introduce a novel framework that can characterize shape changes (morphodynamics) for cell-drug interactions directly from images, and use it to interpret perturbed development of Phakopsora pachyrhizi, the Asian soybean rust crop pathogen. We describe population development over a 2D space of shapes (morphospace) using two models with condition-dependent parameters: a top-down Fokker-Planck model of diffusive development over Waddington-type landscapes, and a bottom-up model of tip growth. We discover a variety of landscapes, describing phenotype transitions during growth, and identify possible perturbations in the tip growth machinery that cause this variation. This demonstrates a widely-applicable integration of unsupervised learning and biophysical modeling.
Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling
Authors: Chen Zhong , Hankey William , Zhao Yue , Groth Jeff , Huang Furong , Wang Hongyan , Campos Alexandre Rosa , Huang Jiaoti , Roeder Robert G. , Wang Qianben 
Published: November 2021

AbstractRNA Polymerase II (Pol II) transcriptional recycling is a mechanism for which the required factors and contributions to overall gene expression levels are poorly understood. We describe an in vitro methodology facilitating unbiased identification of putative RNA Pol II transcriptional recycling factors and quantitative measurement of transcriptional output from recycled transcriptional components. Proof-of-principle experiments identified PAF1 complex components among recycling factors and detected defective transcriptional output from Pol II recycling following PAF1 depletion. Dynamic ChIP-seq confirmed PAF1 silencing triggered defective Pol II recycling in human cells. Prostate tumors exhibited enhanced transcriptional recycling, which was attenuated by antibody-based PAF1 depletion. These findings identify Pol II recycling as a potential target in cancer and demonstrate the applicability of in vitro and cellular transcription assays to characterize Pol II recycling in other disease states.
Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies
Authors: Fenix Aidan M. , Miyaoka Yuichiro , Bertero Alessandro , Blue Steven M. , Spindler Matthew J. , Tan Kenneth K. B. , Perez-Bermejo Juan A. , Chan Amanda H. , Mayerl Steven J. , Nguyen Trieu D. , Russell Caitlin R. , Lizarraga Paweena P. , Truong Annie , So Po-Lin , Kulkarni Aishwarya , Chetal Kashish , Sathe Shashank , Sniadecki Nathan J. , Yeo Gene W. , Murry Charles E. , Conklin Bruce R. , Salomonis Nathan 
Published: November 2021

AbstractMutations in the cardiac splicing factor RBM20 lead to malignant dilated cardiomyopathy (DCM). To understand the mechanism of RBM20-associated DCM, we engineered isogenic iPSCs with DCM-associated missense mutations in RBM20 as well as RBM20 knockout (KO) iPSCs. iPSC-derived engineered heart tissues made from these cell lines recapitulate contractile dysfunction of RBM20-associated DCM and reveal greater dysfunction with missense mutations than KO. Analysis of RBM20 RNA binding by eCLIP reveals a gain-of-function preference of mutant RBM20 for 3′ UTR sequences that are shared with amyotrophic lateral sclerosis (ALS) and processing-body associated RNA binding proteins (FUS, DDX6). Deep RNA sequencing reveals that the RBM20 R636S mutant has unique gene, splicing, polyadenylation and circular RNA defects that differ from RBM20 KO. Super-resolution microscopy verifies that mutant RBM20 maintains very limited nuclear localization potential; rather, the mutant protein associates with cytoplasmic processing bodies (DDX6) under basal conditions, and with stress granules (G3BP1) following acute stress. Taken together, our results highlight a pathogenic mechanism in cardiac disease through splicing-dependent and -independent pathways.
Reversion analysis reveals the in vivo immunogenicity of a poorly MHC I-binding cancer neoepitope
Authors: Ebrahimi-Nik Hakimeh , Moussa Marmar , Englander Ryan P. , Singhaviranon Summit , Michaux Justine , Pak HuiSong , Miyadera Hiroko , Corwin William L. , Keller Grant L. J. , Hagymasi Adam T. , Shcheglova Tatiana V. , Coukos George , Baker Brian M. , Mandoiu Ion I. , Bassani-Sternberg Michal , Srivastava Pramod K. 
Published: November 2021

AbstractHigh-affinity MHC I-peptide interactions are considered essential for immunogenicity. However, some neo-epitopes with low affinity for MHC I have been reported to elicit CD8 T cell dependent tumor rejection in immunization-challenge studies. Here we show in a mouse model that a neo-epitope that poorly binds to MHC I is able to enhance the immunogenicity of a tumor in the absence of immunization. Fibrosarcoma cells with a naturally occurring mutation are edited to their wild type counterpart; the mutation is then re-introduced in order to obtain a cell line that is genetically identical to the wild type except for the neo-epitope-encoding mutation. Upon transplantation into syngeneic mice, all three cell lines form tumors that are infiltrated with activated T cells. However, lymphocytes from the two tumors that harbor the mutation show significantly stronger transcriptional signatures of cytotoxicity and TCR engagement, and induce greater breadth of TCR reactivity than those of the wild type tumors. Structural modeling of the neo-epitope peptide/MHC I pairs suggests increased hydrophobicity of the neo-epitope surface, consistent with higher TCR reactivity. These results confirm the in vivo immunogenicity of low affinity or ‘non-binding’ epitopes that do not follow the canonical concept of MHC I-peptide recognition.
Global distribution, trends, and drivers of flash drought occurrence
Authors: Christian Jordan I. , Basara Jeffrey B. , Hunt Eric D. , Otkin Jason A. , Furtado Jason C. , Mishra Vimal , Xiao Xiangming , Randall Robb M. 
Published: November 2021

AbstractFlash drought is characterized by a period of rapid drought intensification with impacts on agriculture, water resources, ecosystems, and the human environment. Addressing these challenges requires a fundamental understanding of flash drought occurrence. This study identifies global hotspots for flash drought from 1980–2015 via anomalies in evaporative stress and the standardized evaporative stress ratio. Flash drought hotspots exist over Brazil, the Sahel, the Great Rift Valley, and India, with notable local hotspots over the central United States, southwestern Russia, and northeastern China. Six of the fifteen study regions experienced a statistically significant increase in flash drought during 1980–2015. In contrast, three study regions witnessed a significant decline in flash drought frequency. Finally, the results illustrate that multiple pathways of research are needed to further our understanding of the regional drivers of flash drought and the complex interactions between flash drought and socioeconomic impacts.