bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B45: Surveillance of RAS-RAF dynamics in vivo: Tracking activity conformations and drug-induced interactions
Authors: Röck Ruth , Mayrhofer Johanna , Torres-Quesada Omar , Enzler Florian , Troppmair Jakob , Stefan Eduard 
Published: June 2021

Abstract
Live-cell recordings of protein conformations and interactions yield novel mechanistic insights into physiologic and pathologic protein functions. We have developed an adaptable and genetically encoded bioluminescence-based biosensor platform to precisely measure signaling dynamics of full-length RAS GTPases and RAF kinases upon physiologic pathway activation, post-translational modifications, mutagenesis, and drug binding. We have recorded the impact of both patient mutations and bioactive small-molecule binding on kinase conformations and binary interactions of GTP-loaded H, N, KRAS with kinases such as RAF. Systematic profiling of αC-helix-OUT BRAF inhibitors (BRAFi) vemurafenib, dabrafenib, encorafenib, and PLX8394 using the BRAF reporter reporter platform (displaying 10 different patient mutations) revealed differences in drug specificities and efficacies. Unexpectedly, the αC-helix-OUT BRAFi engagement with the catalytic pocket of mutated BRAF stabilized an inactive and intermediate full-length kinase conformation, which provoked the enhancement of binary RAS:RAF interactions. We showed that the interference with RAS interactions and nanoclustering has the potential to antagonize the sequential formation of drug-induced tetrameric RAS:RAF complexes. Recently, we have bioengineered a reporter toolbox for direct in vivo recordings of RAS activity conformations. First, we demonstrated that the wild-type RAS reporter—expressed at levels far below endogenous RAS proteins—responds to physiologic pathway activation. Second, we showed that hot-spot RAS mutations display a similar effect on the intramolecular dynamics. The systematic implementation, combination, and advancement of the GTPase and kinase reporter platform have the potential to be used to identify novel means for regulating or perturbing RAS-RAF-ERK signaling in vivo.
Citation Format: Ruth Röck, Johanna Mayrhofer, Omar Torres-Quesada, Florian Enzler, Jakob Troppmair, Eduard Stefan. Surveillance of RAS-RAF dynamics in vivo: Tracking activity conformations and drug-induced interactions [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B45.
Abstract DP-011: PRE-DIAGNOSIS USE OF MENOPAUSAL HORMONE THERAPY ASSOCIATED WITH BETTER OVARIAN CANCER SURVIVAL
Authors: Lee Alice W. , Peterson Siri , Wiensch Ashley , Pike Malcolm C. , Pearce Celeste L. 
Published: June 2021

Abstract
BACKGROUND: Several lifestyle factors have consistently been associated with survival of ovarian cancer, including body mass index, analgesic medications, physical activity, and smoking. Menopausal hormone therapy (HT), which can comprise of estrogen only (ET) or a combination of estrogen and progestin (EPT), has also been studied for its impact on ovarian survival. Randomized trials as well as a recent meta-analysis have shown better survival for women who took HT after their diagnosis in comparison to women who did not (HR=0.67, 95% CI 0.47-0.97). However, the relationship between use of HT prior to ovarian cancer diagnosis and survival is less clear.
METHODS: Approximately 4,700 ovarian cancer patients across nine population-based studies participating in the Ovarian Cancer Association Consortium (OCAC) were included in our analysis. Information on HT use prior to diagnosis and potential confounders was obtained via phone or in-person interviews. To estimate the effect of pre-diagnostic HT use on ovarian cancer survival, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models with left and right truncation to account for different observation times. Effects by type and duration of HT use as well as disease histotype were also evaluated.
RESULTS: Women who used HT before diagnosis had an 11% decreased risk of death in comparison to those who did not use HT (95% CI 0.82-0.97). Similar effects were observed for both types of HT (HR=0.86, 95% CI 0.75-0.98 for ET and HR=0.89, 95% CI 0.80-0.99 for EPT). In addition, there appeared to be a duration effect with longer HT use conferring better survival (p-trend=0.07 for ET, p-trend=0.003 for EPT). When histotype was considered, the overall decreased risk was driven by serous and mucinous ovarian cancers (HR=0.85, 95% CI 0.77-0.93 and HR=0.54, 95% CI 0.28-1.07, respectively).
CONCLUSIONS: Use of HT after diagnosis also affords a survival advantage based on published observational and clinical trials data. We now report that pre-diagnosis HT use may confer a survival advantage among women with ovarian cancer. Interestingly, use of ET prior to diagnosis is associated with increased risk of ovarian cancer, but better survival among women diagnosed with the disease. These observations taken together demonstrate the complex nature of ovarian cancer.
Citation Format: Alice W. Lee, Siri Peterson, Ashley Wiensch, Malcolm C. Pike, Celeste L. Pearce on behalf of the Ovarian Cancer Association Consortium. PRE-DIAGNOSIS USE OF MENOPAUSAL HORMONE THERAPY ASSOCIATED WITH BETTER OVARIAN CANCER SURVIVAL [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-011.
Abstract NT-099: NOVEL ANTIBODY DRUG CONJUGATE (ADC) AND COMPANION DIAGNOSTICS AGAINST CD248+ CANCER
Authors: Guo Yi , Wang Yujue , Peng Xiaohui , Coukos George , Li Chunsheng 
Published: June 2021

Abstract
Antibodies recognizing specific tumor targets can be used to deliver therapeutic payloads with high degree of specificity. The simultaneous use of antibody against same target for imaging and for therapy, an approach named “theranostics”, offers unique opportunities for precision medicine and rapidly assessing therapeutic response at molecular level. The first example of such antibody-based theranotics is Herceptin in HER2-positive breast cancer: Herceptin is used as companion diagnostic imaging tool as well as the targeted therapy.
To develop effective anti-tumor therapeutics, one needs a robust biomarker, AND a good antibody that can specifically bind to the target. We and others have found one for EOC: CD248/TEM1. It is present at high level in tumor and its microenvironment in EOC and almost absent in normal organs. Importantly, CD248 is expressed by &gt;90% EOC patients on the tumor or tumor vasculature, and its high expression correlates with poor survival. This means that if we can target it, we may destroy tumor but leave normal tissues intact. We also have developed robust antibody against CD248 (78Fc panel, US Patent 61/639,325). We showed that our patented antibodies can find the biomarker and upon binding deliver a payload, for PET imaging, near-infrared optical imaging or therapeutic, to CD248-expressing cells. Different toxin payload, such as auristatin and MD117, were conjugated to the antibody, and such ADCs were tested in vitro and in vivo in mice models. Surprisingly, we found such immunotherapies only directly kill, but also induce significant lymphocyte infiltration into tumors. In addition, tumor rejection was observed upon re-challenging in preclinical models. Such immune activation we observed could in turn sensitizing previously “cold tumor” EOC, to checkpoint inhibitors such as PD-1/CDLA4.
The long term goal is to develop companion diagnostics and antibody-immunotherapy: screening methods (such as antibody-based immunoPET and serum ELISA) to identify patients with EOC that can be treated with anti-CD248 drugs; and develop drugs that are linked to the antibody (such as antibody-drug conjugate) so it can be delivered to the tumor directly to kill. In addition, combined with PD-1 blockade, ADC therapies may exert antitumor immune response to sensitize “cold” tumors that previously resistant to PD-1 therapy.
Citation Format: Yi Guo, Yujue Wang, Xiaohui Peng, George Coukos, Chunsheng Li. NOVEL ANTIBODY DRUG CONJUGATE (ADC) AND COMPANION DIAGNOSTICS AGAINST CD248+ CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-099.
Abstract B24: The macrophage-drug conjugate (MDC) as a “Trojan horse” approach in cancer therapy
Authors: Taciak Bartłomiej , Białasek Maciej , Kucharzewska-Siembieda Paulina , Kiraga Łukasz , Szulc Aleksandra , Górka Emilia , Kubiak Małgorzata , Pilch Zofia , Tonecka Katarzyna , Sas Zuzanna , Braniewska Agata , Cheda Łukasz , Rogulski Zbigniew , Godlewski Michał , Boffi Alberto , Rygiel Tomasz , Król Magdalena 
Published: June 2021

Abstract
Unsatisfactory response of tumors to chemotherapy is mainly related to impaired diffusion of the anticancer drug because of decreased drug uptake due to poor vasculature. Moreover, the drug is not able to penetrate the most hypoxic sites. Cells from these “untreated” sites are responsible for relapse and metastasis. However, these avascular regions attract macrophages that migrate even to areas far away from blood vessels. Therefore, they might constitute a unique delivery system of drug-containing particles to these parts of the tumor mass. A promising example of such particles that could be used is ferritins, whose caged architecture allows for efficient drug encapsulation and whose uptake from macrophage cells has been well demonstrated. Macrophages are also able to specifically and actively transfer these taken-up ferritins (loaded with the anticancer drugs) to cancer cells. This is the new mechanism discovered by our team and named TRAIN (TRAnsfer of Iron-binding proteiN). Thus, there is a possibility to use macrophages to deliver ferritin-encapsulated compounds directly to the tumor cells (MDC technology—Macrophage-Drug Conjugate). This is a completely new and modern approach to anticancer therapy and drug delivery. As such, we expect to be able to precisely administer drugs to the tumor site (even to the hypoxic regions), decreasing side effects of anticancer therapy.
Acknowledgments: This research is founded by the European Research Council, Starting Grant McHAP: 715048. The dissemination of the project is founded by the KNOW (Leading National Research Centre), Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015.
Citation Format: Bartłomiej Taciak, Maciej Białasek, Paulina Kucharzewska-Siembieda, Łukasz Kiraga, Aleksandra Szulc, Emilia Górka, Małgorzata Kubiak, Zofia Pilch, Katarzyna Tonecka, Zuzanna Sas, Agata Braniewska, Łukasz Cheda, Zbigniew Rogulski, Michał Godlewski, Alberto Boffi, Tomasz Rygiel, Magdalena Król. The macrophage-drug conjugate (MDC) as a “Trojan horse” approach in cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B24.
Abstract B66: High-throughput synthesis and screening for tumor-targeting liposomal nanoparticles
Authors: Audeh Mark , Dwarakanath Manali , Hopkins Michael , Knudson Alisha , Kwok Sally , Morton Stephen , Peck Nikki , Ruckh Tim , Sanowar Sarah , Scott Zach , Thana Peter , Tong Gary , Topol Aaron , Vitari Alberto C , Vaisberg Eugeni , Wang Jane , Wong Stanley 
Published: June 2021

Abstract
The identification of therapeutic nanoparticles formulation with preferential distribution to the tumor microenvironment remains an unsolved challenge. We have developed a high-throughput synthesis and screening platform to discover novel tumor-targeting liposomal nanoparticles. Over 1,000 unique liposomal formulations were synthesized using a combinatorial approach. The characterization of physicochemical properties (e.g., size, charge and stability) allowed the prioritization of ~500 formulations further profiled with in vitro cell-based assays (e.g., cell binding, cytotoxicity and cell barrier crossing). A subset of formulations with diverse properties was selected to create a library of 47 DNA-barcoded nanoparticles. The pharmacokinetics and biodistribution of the formulations library were measured in tumor xenografts mouse models in a highly multiplexed fashion by sequencing the DNA barcodes. The established synthesis and screening platform provides an effective approach to identify novel liposomal formulations with improved tumor and tissue distribution profile.
Note: This abstract was not presented at the conference.
Citation Format: Mark Audeh, Manali Dwarakanath, Michael Hopkins, Alisha Knudson, Sally Kwok, Stephen Morton, Nikki Peck, Tim Ruckh, Sarah Sanowar, Zach Scott, Peter Thana, Gary Tong, Aaron Topol, Alberto C Vitari, Eugeni Vaisberg, Jane Wang, Stanley Wong. High-throughput synthesis and screening for tumor-targeting liposomal nanoparticles [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B66.
Microvascular Disease and Incident Heart Failure Among Individuals With Type 2 Diabetes Mellitus
Authors: Kaze Arnaud D. , Santhanam Prasanna , Erqou Sebhat , Ahima Rexford S. , Bertoni Alain , Echouffo‐Tcheugui Justin B. 
Published: June 2021

Background
Microvascular disease (MVD) is a potential contributor to the pathogenesis of diabetes mellitus–related cardiac dysfunction. However, there is a paucity of data on the link between MVD and incident heart failure (HF) in type 2 diabetes mellitus. We examined the association of MVD with incident HF in adults with type 2 diabetes mellitus.

Methods and Results
A total of 4095 participants with type 2 diabetes mellitus and free of HF were assessed for diabetes mellitus–related MVD including nephropathy, retinopathy, or neuropathy at baseline in the Look AHEAD (Action for Health in Diabetes) study. Incident HF events were prospectively assessed and adjudicated using hospital and death records. Cox models were used to generate hazard ratios and 95% CIs for HF. Of 4095 participants, 34.8% (n=1424) had MVD, defined as the presence of ≥1 of nephropathy, retinopathy, or neuropathy at baseline. Over a median of 9.7 years, there were 117 HF events. After adjusting for relevant confounders, participants with MVD had a 2.5‐fold higher risk of incident HF than those without MVD (hazard ratio, 2.54; 95% CI, 1.73–3.75). This association remained significant after additional adjustment for interval development of coronary artery disease (hazard ratio, 2.42; 95% CI, 1.64–3.57). The hazard ratios for HF by type of MVD were 2.22 (95% CI, 1.51–3.27), 1.30 (95% CI, 0.72–2.36), and 1.33 (95% CI, 0.86–2.07) for nephropathy, retinopathy, and neuropathy, respectively.

CONCLUSIONS
MVD is associated with an excess HF risk in individuals with type 2 diabetes mellitus after adjusting for other known risk factors. Our findings underscore the contribution of MVD to the development of diabetes mellitus–related HF.

REGISTRATION: URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00017953.
Linking Shrimp Farmers and Food Processors
Authors: Schwabe Julian , Nguyen Chung Van , Hassler Markus 
Published: June 2021

Abstract
This study explores the barriers faced by white shrimp farmers in Vietnam in linking directly with food processing companies. The shrimp sector in Vietnam is still characterised by highly informal structures, weak implementation of food safety regulations and a lack of expertise among farmers to comply with international standards. The Vietnamese government anticipates modernising shrimp production and enabling farmers to achieve the quality standards of international retailers. While international food processing companies have established locations in Vietnam to serve international markets, farmers often lack the resources and expertise to comply with their requirements. The main challenges are related to infrastructure for transport and payment transfers, risk management and overcoming established production routines which are mostly based on tacit knowledge and experience. Hence, efforts are needed to improve infrastructures, establish risk management tools for farmers and promote successful cases which can act as guiding examples for adapting white shrimp production.
The Concepts and Ideas of ‘Spirituality’ Within Worldviews of Alternative Religiosities in the Post-Communist Region: Vissarionites and Anastasians
Authors: Pranskevičiūtė-Amoson Rasa 
Published: June 2021

Abstract
The article presents research on contemporary religiosities related to individuality and subcultural features, influenced by the processes of social change and religious diversification in the post-communist region. Its aim is to discuss individual and communal thinking (orientated to esotericism, magic, and ecology) typical for representatives of two nature-based spirituality movements—Vissarionites and Anastasians, which is expressed through concepts of New Age spirituality of Oriental origin. The concepts of energy, non-violence, vegetarianism, karma, and reincarnation are used in both movements and appear as an example of how such concepts arrived through Western cultural influences, transformed, and took root in the post-communist cultural context of New Age spirituality. The findings are based on data obtained from fieldwork in 2004–2015, including participant observation and interviews with respondents in the Baltic states and Russia.
Seasonal Variation of the Surface Kuroshio Intrusion into the South China Sea Evidenced by Satellite Geostrophic Streamlines
Authors: Zhong Yisen , Zhou Meng , Waniek Joanna J. , Zhou Lei , Zhang Zhaoru 
Published: June 2021

AbstractThe long-term satellite altimeter and reanalysis data show that large seasonal variations are associated with geostrophic Kuroshio intrusion, but not with the current intensity, width and axis position east of Philippine. To address this issue, we examine the seasonal variability of surface intrusion patterns by a new streamline-based method. The along-streamline analysis reveals that the seasonality of geostrophic intrusion is only attributed to the cyclonic shear part of the flow, while the anticyclonic shear part always leaps across the Luzon Strait. A possible physical mechanism is proposed to accommodate these seasonal characteristics based on globally the vorticity (torque work) balance between the basin-wide negative wind stress curl and the positive vorticity fluxes induced by the lateral wall, as well as locally loss of balance between the torques of frictional stresses and normal stresses owing to the boundary gap. Through modifying the nearshore sea surface level, the northeasterly/southeasterly monsoon increases/decreases the positive vorticity fluxes in response to global vorticity balance, and simultaneously amplifies/alleviates the local imbalance by enhancing/reducing the positive frictional stress torque within the cyclonic shear layer. Therefore, in winter when the positive torque is large enough, the Kuroshio splits and the intrusion occurs, while in summer the stress torque is so weak that the entire current keeps flowing north.
Wind- and Wave-driven Ocean Surface Boundary Layer in a Frontal Zone: Roles of Submesoscale Eddies and Ekman-Stokes Transport
Authors: Yuan Jianguo , Liang Jun-Hong 
Published: June 2021

AbstractLarge-eddy simulations are used to investigate the influence of a horizontal frontal zone, represented by a stationary uniform background horizontal temperature gradient, on the wind- and wave-driven ocean surface boundary layers. In a frontal zone, the temperature structure, the ageostrophic mean horizontal current, and the turbulence in the ocean surface boundary layer all change with the relative angle among the wind and the front. The net heating and cooling of the boundary layer could be explained by the depth-integrated horizontal advective buoyancy flux, called the Ekman Buoyancy Flux (or the Ekman-Stokes Buoyancy Flux if wave effects are included). However, the detailed temperature profiles are also modulated by the depth-dependent advective buoyancy flux and submesoscale eddies. The surface current is deflected less (more) to the right of the wind and wave when the depth-integrated advective buoyancy flux cools (warms) the ocean surface boundary layer. Horizontal mixing is greatly enhanced by submesoscale eddies. The eddy-induced horizontal mixing is anisotropic and is stronger to the right of the wind direction. Vertical turbulent mixing depends on the superposition of the geostrophic and ageostrophic current, the depth-dependent advective buoyancy flux, and submesoscale eddies.
Development of a track-pattern-based medium-range tropical cyclone forecasting system for the western North Pacific
Authors: Cheung Hung Ming , Ho Chang-Hoi , Chang Minhee , Kim Dasol , Kim Jinwon , Choi Woosuk 
Published: June 2021

AbstractDespite tremendous advancements in dynamical models for weather forecasting, statistical models continue to offer various possibilities for tropical cyclone (TC) track forecasting. Herein, a track-pattern-based approach was developed to predict a TC track for a lead time of 6–8 days over the western North Pacific (WNP), utilizing historical tracks in conjunction with dynamical forecasts. It is composed of four main steps: (1) clustering historical tracks similar to that of an operational five-day forecast in their early phase into track patterns, and calculating the daily mean environmental fields (500-hPa geopotential height and steering flow) associated with each track; (2) deriving the two environmental variables forecasted by dynamical models; (3) evaluating pattern correlation coefficients between the two environmental fields from step (1) and those from dynamical model for a lead times of 6–8 days; and (4) producing the final track forecast based on relative frequency maps obtained from the historical tracks in step (1) and the pattern correlation coefficients obtained from step (3). TCs that formed in the WNP and lasted for at least seven days, during the 9-year period 2011–2019 were selected to verify the resulting track-pattern-based forecasts. In addition to the performance comparable to dynamical models under certain conditions, the track-pattern-based model is inexpensive, and can consistently produce forecasts over large latitudinal or longitudinal ranges. Machine learning techniques can be implemented to incorporate non-linearity in the present model for improving medium-range track forecasts.