bluuebunny/crossref_metadata_2025_split huggingface dataset:
The modern geological survey: a model for research, innovation, synthesis. A USGS perspective
Authors: Kimball Suzette , Goldhaber M. , Baron J. , Labson V. 
Published: March 2020

Abstract
Geological surveys have long filled the role of providing Earth system science data and knowledge. These functions are increasingly complicated by accelerating environmental and societal change. Here we describe the US Geological Survey (USGS) response to these evolving conditions. Underpinning the USGS approach is the recognition that many of the issues facing the USA and the world involve interaction among geological, hydrological and biological processes, and how these interactions in turn affect society. Therefore, a goal of USGS planning is fostering interdisciplinary science. This focus is occurring in part through implementation of the recommendations of strategic planning teams. The USGS has also put in place groups building a broad information technology infrastructure as well as identifying and disseminating new Earth science research tools. In addition, the USGS has established an analysis and synthesis centre that brings together groups of scientists who address interdisciplinary Earth system science issues. The goal is for these building blocks to evolve towards a comprehensive USGS data and knowledge platform – EarthMAP (Earth Monitoring, Assessment, and Projection). We also recognize that the modern geological survey must be a member of a community of geological surveys contributing data to a global database of three-dimensional biogeophysical observations and interpretations.
IL33 Is a Key Driver of Treatment Resistance of Cancer
Authors: Kudo-Saito Chie , Miyamoto Takahiro , Imazeki Hiroshi , Shoji Hirokazu , Aoki Kazunori , Boku Narikazu 
Published: March 2020

Abstract

Recurrence and treatment resistance are major causes of cancer-associated death. There has been a growing interest in better understanding epithelial–mesenchymal transition, stemness of cancer cells, and exhaustion and dysfunction of the immune system for which numerous genomic, proteomic, microenvironmental, and immunologic mechanisms have been demonstrated. However, practical treatments for such patients have not yet been established. Here we identified IL33 as a key driver of polyploidy, followed by rapid proliferation after treatment. IL33 induction transformed tumor cells into polyploid giant cells, showing abnormal cell cycle without cell division accompanied by Snail deregulation and p53 inactivation; small progeny cells were generated in response to treatment stress. Simultaneously, soluble IL33 was released from tumor cells, leading to expansion of receptor ST2-expressing cells including IL17RB+GATA3+ cells, which promoted tumor progression and metastasis directly and indirectly via induction of immune exhaustion and dysfunction. Blocking IL33 with a specific mAb in murine IL33+ metastatic tumor models abrogated negative consequences and successfully elicited antitumor efficacy induced by other combined treatments. Ex vivo assays using tumor tissues and peripheral blood mononuclear cells of patients with cancer validated the clinical relevancy of these findings. Together, these data suggest that targeting the IL33-ST2 axis is a promising strategy for diagnosis and treatment of patients likely to be resistant to treatments in the clinical settings.

Significance:
These findings indicate that the functional role of IL33 in cancer polyploidy contributes to intrinsic and extrinsic mechanisms underlying treatment failure.
Blockade of β-Catenin–Induced CCL28 Suppresses Gastric Cancer Progression via Inhibition of Treg Cell Infiltration
Authors: Ji Lu , Qian Wei , Gui Liming , Ji Zhongzhong , Yin Pan , Lin Guan Ning , Wang You , Ma Bin , Gao Wei-Qiang 
Published: March 2020

Abstract

Dysregulation of Wnt/β-catenin signaling is frequently observed in human gastric cancer. Elucidation of the tumor immune microenvironment is essential for understanding tumorigenesis and for the development of immunotherapeutic strategies. However, it remains unclear how β-catenin signaling regulates the tumor immune microenvironment in the stomach. Here, we identify CCL28 as a direct transcriptional target gene of β-catenin/T-cell factor (TCF). Protein levels of β-catenin and CCL28 positively correlated in human gastric adenocarcinoma. β-Catenin–activated CCL28 recruited regulatory T (Treg) cells in a transwell migration assay. In a clinically relevant mouse gastric cancer model established by Helicobacter (H.) felis infection and N-methyl-N-nitrosourea (MNU) treatment, inhibition of β-catenin/TCF activity by a pharmacologic inhibitor iCRT14 suppressed CCL28 expression and Treg cell infiltration in the stomach. Moreover, an anti-CCL28 antibody attenuated Treg cell infiltration and tumor progression in H. felis/MNU mouse models. Diphtheria toxin–induced Treg cell ablation restrained gastric cancer progression in H. felis/MNU-treated DEREG (Foxp3-DTR) mice, clarifying the tumor-promoting role of Treg cells. Thus, the β-catenin–CCL28–Treg cell axis may serve as an important mechanism for immunosuppression of the stomach tumor microenvironment. Our findings reveal an immunoregulatory role of β-catenin signaling in stomach tumors and highlight the therapeutic potential of CCL28 blockade for the treatment of gastric cancer.

Significance:
These findings demonstrate an immunosuppressive role of tumor-intrinsic β-catenin signaling and the therapeutic potential of CCL28 blockade in gastric cancer.
Small-Cell Carcinoma of the Ovary, Hypercalcemic Type–Genetics, New Treatment Targets, and Current Management Guidelines
Authors: Tischkowitz Marc , Huang Sidong , Banerjee Susana , Hague Jennifer , Hendricks William P.D. , Huntsman David G. , Lang Jessica D. , Orlando Krystal A. , Oza Amit M. , Pautier Patricia , Ray-Coquard Isabelle , Trent Jeffrey M. , Witcher Michael , Witkowski Leora , McCluggage W. Glenn , Levine Douglas A. , Foulkes William D. , Weissman Bernard E. 
Published: March 2020

AbstractSmall-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian malignancy. In almost all cases, it is associated with somatic and often germline pathogenic variants in SMARCA4, which encodes for the SMARCA4 protein (BRG1), a subunit of the SWI/SNF chromatin remodeling complex. Approximately 20% of human cancers possess pathogenic variants in at least one SWI/SNF subunit. Because of their role in regulating many important cellular processes including transcriptional control, DNA repair, differentiation, cell division, and DNA replication, SWI/SNF complexes with mutant subunits are thought to contribute to cancer initiation and progression. Fewer than 500 cases of SCCOHT have been reported in the literature and approximately 60% are associated with hypercalcemia. SCCOHT primarily affects females under 40 years of age who usually present with symptoms related to a pelvic mass. SCCOHT is an aggressive cancer, with long-term survival rates of 30% in early-stage cases. Although various treatment approaches have been proposed, there is no consensus on surveillance and therapeutic strategy. An international group of multidisciplinary clinicians and researchers recently formed the International SCCOHT Consortium to evaluate current knowledge and propose consensus surveillance and therapeutic recommendations, with the aim of improving outcomes. Here, we present an overview of the genetics of this cancer, provide updates on new treatment targets, and propose management guidelines for this challenging cancer.
Integrative Omics Analysis Reveals Soluble Cadherin-3 as a Survival Predictor and an Early Monitoring Marker of EGFR Tyrosine Kinase Inhibitor Therapy in Lung Cancer
Authors: Hsiao Ting-Feng , Wang Chih-Liang , Wu Yi-Cheng , Feng Hsiang-Pu , Chiu Yen-Chuan , Lin Hao-Yu , Liu Ko-Jiunn , Chang Gee-Chen , Chien Kun-Yi , Yu Jau-Song , Yu Chia-Jung 
Published: March 2020

Abstract

Purpose:
EGFR tyrosine kinase inhibitors (EGFR-TKI) benefit patients with advanced lung adenocarcinoma (ADC) harboring activating EGFR mutations. We aimed to identify biomarkers to monitor and predict the progression of patients receiving EGFR-TKIs via a comprehensive omic analysis.

Experimental Design:
We applied quantitative proteomics to generate the TKI resistance–associated pleural effusion (PE) proteome from patients with ADC with or without EGFR-TKI resistance. Candidates were selected from integrated genomic and proteomic datasets. The PE (n = 33) and serum (n = 329) levels of potential biomarkers were validated with ELISAs. Western blotting was applied to detect protein expression in tissues, PEs, and a cell line. Gene knockdown, TKI treatment, and proliferation assays were used to determine EGFR-TKI sensitivity. Progression-free survival (PFS) and overall survival (OS) were assessed to evaluate the prognostic values of the potential biomarkers.

Results:
Fifteen proteins were identified as potential biomarkers of EGFR-TKI resistance. Cadherin-3 (CDH3) was overexpressed in ADC tissues compared with normal tissues. CDH3 knockdown enhanced EGFR-TKI sensitivity in ADC cells. The PE level of soluble CDH3 (sCDH3) was increased in patients with resistance. The altered sCDH3 serum level reflected the efficacy of EGFR-TKI after 1 month of treatment (n = 43). Baseline sCDH3 was significantly associated with PFS and OS in patients with ADC after EGFR-TKI therapy (n = 76). Moreover, sCDH3 was positively associated with tumor stage in non–small cell lung cancer (n = 272).

Conclusions:
We provide useful marker candidates for drug resistance studies. sCDH3 is a survival predictor and real-time indicator of treatment efficacy in patients with ADC treated with EGFR-TKIs.
A Randomized Phase II Preoperative Study of Autophagy Inhibition with High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients
Authors: Zeh Herbert J. , Bahary Nathan , Boone Brian A. , Singhi Aatur D. , Miller-Ocuin Jennifer Lee , Normolle Daniel P. , Zureikat Amer H. , Hogg Melissa E. , Bartlett David L. , Lee Kenneth K. , Tsung Allan , Marsh J. Wallis , Murthy Pranav , Tang Daolin , Seiser Natalie , Amaravadi Ravi K. , Espina Virginia , Liotta Lance , Lotze Michael T. 
Published: March 2020

Abstract

Purpose:
We hypothesized that autophagy inhibition would increase response to chemotherapy in the preoperative setting for patients with pancreatic adenocarcinoma. We performed a randomized controlled trial to assess the autophagy inhibitor hydroxychloroquine in combination with gemcitabine and nab-paclitaxel.

Patients and Methods:
Participants with potentially resectable tumors were randomized to two cycles of nab-paclitaxel and gemcitabine (PG) alone or with hydroxychloroquine (PGH), followed by resection. The primary endpoint was histopathologic response in the resected specimen. Secondary clinical endpoints included serum CA 19-9 biomarker response and margin negative R0 resection. Exploratory endpoints included markers of autophagy, immune infiltrate, and serum cytokines.

Results:
Thirty-four patients in the PGH arm and 30 in the PG arm were evaluable for the primary endpoint. The PGH arm demonstrated statistically improved Evans grade histopathologic responses (P = 0.00016), compared with control. In patients with elevated CA 19-9, a return to normal was associated with improved overall and recurrence-free survival (P &lt; 0.0001). There were no differences in serious adverse events between arms and chemotherapy dose number was equivalent. The PGH arm had greater evidence of autophagy inhibition in their resected specimens (increased SQSTM1, P = 0.027, as well as increased immune cell tumor infiltration, P = 0.033). Overall survival (P = 0.59) and relapse-free survival (P = 0.55) did not differ between the two arms.

Conclusions:
The addition of hydroxychloroquine to preoperative gemcitabine and nab-paclitaxel chemotherapy in patients with resectable pancreatic adenocarcinoma resulted in greater pathologic tumor response, improved serum biomarker response, and evidence of autophagy inhibition and immune activity.
Sex-Specific Management in Patients With Acute Myocardial Infarction and Cardiogenic Shock
Authors: Rubini Gimenez Maria , Zeymer Uwe , Desch Steffen , de Waha-Thiele Suzanne , Ouarrak Taoufik , Poess Janine , Meyer-Saraei Roza , Schneider Steffen , Fuernau Georg , Stepinska Janina , Huber Kurt , Windecker Stephan , Montalescot Gilles , Savonitto Stefano , Jeger Raban V. , Thiele Holger 
Published: March 2020

Background:
Women are more likely to suffer and die from cardiogenic shock (CS) as the most severe complication of acute myocardial infarction. Data concerning optimal management for women with CS are scarce. Aim of this study was to better define characteristics of women experiencing CS and to the influence of sex on different treatment strategies.

Methods:
In the CULPRIT-SHOCK trial (The Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock), patients with CS complicating acute myocardial infarction and multivessel coronary artery disease were randomly assigned to one of the following revascularization strategies: either percutaneous coronary intervention of the culprit-lesion-only or immediate multivessel percutaneous coronary intervention. Primary end point was composite of death from any cause or severe renal failure leading to renal replacement therapy within 30 days. We investigated sex-specific differences in general and according to the revascularization strategies.

Results:

Among all 686 randomized patients included in the analysis, 24% were women. Women were older and had more often diabetes mellitus and renal insufficiency, whereas they had less often history of previous acute myocardial infarction and smoking. After 30 days, the primary clinical end point was not significantly different between groups (56% women versus 49% men; odds ratio, 1.29 [95% CI, 0.91–1.84];
P
=0.15). There was no interaction between sex and coronary revascularization strategy regarding mortality and renal failure (
P
interaction
=0.11). The primary end point occurred in 56% of women treated by the culprit-lesion-only strategy versus 42% men, whereas 55% of women and 55% of men in the multivessel percutaneous coronary intervention group.

Conclusions:
Although women presented with a different risk profile, mortality and renal replacement were similar to men. Sex did not influence mortality and renal failure according to the different coronary revascularization strategies. Based on these data, women and men presenting with CS complicating acute myocardial infarction and multivessel coronary artery disease should not be treated differently. However, further randomized trials powered to address potential sex-specific differences in CS are still necessary.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01927549.
Characteristics of Model Tropical Cyclone Climatology and the Large-Scale Environment
Authors: Camargo Suzana J. , Giulivi Claudia F. , Sobel Adam H. , Wing Allison A. , Kim Daehyun , Moon Yumin , Strong Jeffrey D. O. , Del Genio Anthony D. , Kelley Maxwell , Murakami Hiroyuki , Reed Kevin A. , Scoccimarro Enrico , Vecchi Gabriel A. , Wehner Michael F. , Zarzycki Colin , Zhao Ming 
Published: March 2020

AbstractHere we explore the relationship between the global climatological characteristics of tropical cyclones (TCs) in climate models and the modeled large-scale environment across a large number of models. We consider the climatology of TCs in 30 climate models with a wide range of horizontal resolutions. We examine if there is a systematic relationship between the climatological diagnostics for the TC activity [number of tropical cyclones (NTC) and accumulated cyclone energy (ACE)] by hemisphere in the models and the environmental fields usually associated with TC activity, when examined across a large number of models. For low-resolution models, there is no association between a conducive environment and TC activity, when integrated over space (tropical hemisphere) and time (all years of the simulation). As the model resolution increases, for a couple of variables, in particular vertical wind shear, there is a statistically significant relationship in between the models’ TC characteristics and the environmental characteristics, but in most cases the relationship is either nonexistent or the opposite of what is expected based on observations. It is important to stress that these results do not imply that there is no relationship between individual models’ environmental fields and their TC activity by basin with respect to intraseasonal or interannual variability or due to climate change. However, it is clear that when examined across many models, the models’ mean state does not have a consistent relationship with the models’ mean TC activity. Therefore, other processes associated with the model physics, dynamical core, and resolution determine the climatological TC activity in climate models.
Composite Synoptic-Scale Environments Conducive to North American Polar–Subtropical Jet Superposition Events
Authors: Winters Andrew C. , Keyser Daniel , Bosart Lance F. , Martin Jonathan E. 
Published: March 2020

AbstractA polar–subtropical jet superposition represents a dynamical and thermodynamic environment conducive to the production of high-impact weather. Prior work indicates that the synoptic-scale environments that support the development of North American jet superpositions vary depending on the case under consideration. This variability motivates an analysis of the range of synoptic–dynamic mechanisms that operate within a double-jet environment to produce North American jet superpositions. This study identifies North American jet superposition events during November–March 1979–2010 and subsequently classifies those events into three characteristic event types. “Polar dominant” events are those during which only the polar jet is characterized by a substantial excursion from its climatological latitude band, “subtropical dominant” events are those during which only the subtropical jet is characterized by a substantial excursion from its climatological latitude band, and “hybrid” events are those characterized by a mutual excursion of both jets from their respective climatological latitude bands. The analysis indicates that North American jet superposition events occur most often during November and December, and subtropical dominant events are the most frequent event type for all months considered. Composite analyses constructed for each event type reveal the consistent role that descent plays in restructuring the tropopause beneath the jet-entrance region prior to jet superposition. The composite analyses further show that surface cyclogenesis and widespread precipitation lead the development of subtropical dominant events and contribute to jet superposition via their associated divergent circulations and diabatic heating, whereas surface cyclogenesis and widespread precipitation tend to peak at the time of superposition and well downstream of polar dominant events.
Thunderstorm Cloud-Type Classification from Space-Based Lightning Imagers
Authors: Peterson Michael , Rudlosky Scott , Zhang Daile 
Published: March 2020

AbstractThe organization and structure of thunderstorms determines the extent and severity of their hazards to the general public and their consequences for the Earth system. Distinguishing vigorous convective regions that produce heavy rain and hail from adjacent regions of stratiform clouds or overhanging anvil clouds that produce light to no rainfall is valuable in operations and physical research. Cloud-type algorithms that partition convection from stratiform regions have been developed for space-based radar, passive microwave, and now Geostationary Operational Environmental Satellites (GOES) Advanced Baseline Imager (ABI) multispectral products. However, there are limitations for each of these products including temporal availability, spatial coverage, and the degree to which they based on cloud microphysics. We have developed a cloud-type algorithm for GOES Geostationary Lightning Mapper (GLM) observations that identifies convective/nonconvective regions in thunderstorms based on signatures of interactions with nonconvective charge structures in the lightning flash data. The GLM sensor permits a rapid (20 s) update cycle over the combinedGOES-16–GOES-17domain across all hours of the day. Storm regions that do not produce lightning will not be classified by our algorithm, however. The GLM cloud-type product is intended to provide situational awareness of electrified nonconvective clouds and to complement other cloud-type retrievals by providing a contemporary assessment tied to lightning physics. We propose that a future combined ABI–GLM cloud-type algorithm would be a valuable product that could draw from the strengths of each instrument and approach.
Force Anticipation and Its Potential Implications on Feedforward and Feedback Human Motor Control
Authors: Kimpara Hideyuki , Mbanisi Kenechukwu C. , Li Zhi , Troy Karen L. , Prokhorov Danil , Gennert Michael A. 
Published: March 2020

Objective To investigate the effects of human force anticipation, we conducted an experimental load-pushing task with diverse combinations of informed and actual loading weights. Background Human motor control tends to rely upon the anticipated workload to plan the force to exert, particularly in fast tasks such as pushing objects in less than 1 s. The motion and force responses in such tasks may depend on the anticipated resistive forces, based on a learning process. Method Pushing performances of 135 trials were obtained from 9 participants. We varied the workload by changing the masses from 0.2 to 5 kg. To influence anticipation, participants were shown a display of the workload that was either correct or incorrect. We collected the motion and force data, as well as electromyography (EMG) signals from the actively used muscle groups. Results Overanticipation produced overshoot performances in more than 80% of trials. Lighter actual workloads were also associated with overshoot. Pushing behaviors with heavier workloads could be classified into feedforward-dominant and feedback-dominant responses based on the timing of force, motion, and EMG responses. In addition, we found that the preceding trial condition affected the performance of the subsequent trial. Conclusion Our results show that the first peak of the pushing force increases consistently with anticipatory workload. Application This study improves our understanding of human motion control and can be applied to situations such as simulating interactions between drivers and assistive systems in intelligent vehicles.