bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sounding Robots: Design and Evaluation of Auditory Displays for Unintentional Human-robot Interaction
Authors: Orthmann Bastian , Leite Iolanda , Bresin Roberto , Torre Ilaria 
Published: August 2023

Non-verbal communication is important in HRI, particularly when humans and robots do not need to actively engage in a task together, but rather they co-exist in a shared space. Robots might still need to communicate states such as urgency or availability, and where they intend to go, to avoid collisions and disruptions. Sounds could be used to communicate such states and intentions in an intuitive and non-disruptive way. Here, we propose a multi-layer classification system for displaying various robot information simultaneously via sound. We first conceptualise which robot features could be displayed (robot size, speed, availability for interaction, urgency, and directionality); we then map them to a set of audio parameters. The designed sounds were then evaluated in five online studies, where people listened to the sounds and were asked to identify the associated robot features. The sounds were generally understood as intended by participants, especially when they were evaluated one feature at a time, and partially when they were evaluated two features simultaneously. The results of these evaluations suggest that sounds can be successfully used to communicate robot states and intended actions implicitly and intuitively.
Abstract A009: Therapeutic targeting of P2 × 4 receptor and mitochondrial metabolism in clear cell renal carcinoma
Authors: Orsi Sabrina , Rupert Christopher , Pili Roberto , De Nigris Filomena 
Published: August 2023

Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer. Large scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of renal carcinoma and have correlated mitochondrial activity with poor survival in a subset of patients. Our data suggest that oxo-phosphorylation is the main source of tumor-derived ATP in ccRCC expressing P2XR4, which exerts a critical impact on tumor energy metabolism and mitochondrial activity. Seahorse experiments showed that P2XR4 inhibition by 5-BDBD, a potent selective antagonist, caused a rapid dose-dependent reduction of mitochondrial activity and lysosome damage. Moreover, prolonged mitochondrial failure induced by 5-BDBD or P2XR4 silencing was associated with increased oxygen radical species, changes in mitochondrial permeability (i.e. opening of the transition pore complex, dissipation of membrane potential and calcium overload), and cell death via both necrosis and apoptosis. P2XR4 pharmacological inhibition was associated with a significant anti-tumor effect both in vitro and in vivo, as shown in ccRCC cell lines, patient-derived organoids and in murine xenografts. Interestingly, higher mitochondrial activity was associated with greater sensitivity to P2XR4 inhibition. Overall, our results suggest that the perturbed balance between lysosomal integrity and mitochondrial activity induced by P2XR4 inhibition may represent a new therapeutic strategy for a subset of renal carcinoma patients.
Citation Format: Sabrina Orsi, Christopher Rupert, Roberto Pili, Filomena De Nigris. Therapeutic targeting of P2 × 4 receptor and mitochondrial metabolism in clear cell renal carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr A009.
Abstract B033: Targeting acquired resistance to HIF2α inhibition in kidney cancer
Authors: Zhao Fangzhou , Simon Jeremy , Zhang Qing 
Published: August 2023

Abstract
Recently, a HIF-2α inhibitor MK-6482 was developed and approved by FDA to treat certain patients with VHL disease-associated RCC. However, in preclinical studies, both intrinsic and adaptive resistance to this drug was reported, which highlights the necessity of uncovering the mechanisms underlying drug resistance and developing alternative treatments for HIF-2α inhibitor-resistant patients. To this end, we established several 786-O cell lines that are resistant to PT2399 (analog of MK-6482) treatment. To characterize the differences between sensitive and resistant cell lines, we performed RNA sequencing, Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and CUT&RUN sequencing experiments. Through integrative analyses of all sequencing data, we identified a series of candidate genes which might contribute to the acquirement of drug resistance for further validation. We identified 2'-5'-oligoadenylate synthetase 2 (OAS2) as one of the candidate genes exhibiting both significant upregulation in RNA level and dramatically increased chromatin accessibility in the promoter region in resistant lines comparing to sensitive lines. We further validated the upregulation of OAS2 mRNA level as well as protein level in all resistant clones by RT-qPCR and western blot, respectively. OAS2 belongs to 2-5A synthetase family, which is involved in the activation of latent RNase L and degradation of viral RNA during innate immune response to viral infection. Interestingly, the other 3 members in this protein family, OAS1, OAS3 and OASL, are also significantly upregulated at RNA level in resistant cell lines, although the upregulation of chromatin accessibility is modest. Furthermore, OAS2, along with the other 3 family members, all show increased expression levels in ccRCC tumor tissues comparing to normal tissues. Therefore, we hypothesize that OAS2 protein promotes ccRCC cell proliferation under HIF-2α inhibitor treatment, thus contributing to the adaptive resistance to HIF-2α inhibitor. We will test this hypothesis through a series of loss-of-function and gain-of-function experiments, while continuing to investigate other candidate genes.
Citation Format: Fangzhou Zhao, Jeremy Simon, Qing Zhang. Targeting acquired resistance to HIF2α inhibition in kidney cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr B033.
Abstract IA017: Metabolic reprogramming and kidney cancer progression
Authors: DeBerardinis Ralph J. 
Published: August 2023

Abstract
Many human diseases, including cancer, involve alterations of cellular metabolism caused either directly or indirectly by mutations in genes that regulate the metabolic network. In cancer, reprogrammed metabolic activities arising from mutations in tumor suppressors and oncogenes are thought to contribute both to cancer initiation and progression, particularly metastasis. In clear cell renal cell carcinoma, as with many other kinds of cancer, mortality is largely dictated by metastatic dissemination. It is therefore of interest to identify aspects of metabolic reprogramming that promote metastasis in ccRCC patients. We used a multidisciplinary clinical approach to infuse 13C-labeled nutrients during surgical tumor resection in ccRCC patients. Compared to the adjacent kidney, ccRCCs displayed suppressed labelling of tricarboxylic acid (TCA) cycle intermediates, both in vivo and in organotypic slices cultured ex vivo, indicating that suppressed labeling is a tissue intrinsic property of these tumors. Infusions of 13C-acetate and 13C-glutamine in patients, coupled with metabolic analysis of mitochondria isolated from kidney and tumor tissue, revealed primary defects in mitochondrial function in human ccRCC. However, ccRCC metastases unexpectedly had enhanced labeling of TCA cycle intermediates compared to primary ccRCCs, indicating a divergent metabolic program during ccRCC metastasis in patients. Using a syngeneic RCC mouse model capable of spontaneous metastasis from the kidney, we found that inhibiting oxidative phosphorylation reduced metastasis to the lung without impacting tumor growth in the kidney. In human ccRCC cells, stimulating respiration was sufficient to promote metastatic colonization in the lung. Altogether, these findings indicate that metabolic properties evolve during human ccRCC progression, and suggest that mitochondrial respiration may be limiting for ccRCC metastasis but not for ccRCC growth at the site of origin.
Citation Format: Ralph J. DeBerardinis. Metabolic reprogramming and kidney cancer progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA017.
Abstract IA025: The cell of origin is the dominant constraint in evolution of VHL related neoplasms
Authors: Shepherd Scott , Coulton Alex , Vocke Cathy , Ricketts Chris , Linehan Marston , Turajlic Samra 
Published: August 2023

Abstract
Cancer is an evolutionary process, and an evolutionary framework can be used to decipher cancer initiation, progression and treatment resistance. In the context of VHL disease with repeat evolution of malignancies across different tissue contexts we can examine the factors that constrain tumour evolution. In the largest analysis of VHL-related tumours to date (1321 tumours across 132 patients), we observe the second hits on the background of germline VHL mutation vary and include loss of chromosome 3p, narrow deletion of VHL locus, VHL mutation or methylation. Pheochromocytomas and paragangliomas (PPGL) and solid renal tumours show a higher frequency of 3p loss, while pancreatic neuroendocrine tumors (PNETs) and renal cysts, exhibited a higher frequency of somatic VHL mutations, without 3p loss. Tumour size and progression were contingent on the nature of the second hit, suggesting potential evolutionary "dead-ends" where the tumor initiating event does not involve 3p loss. The type of germline VHL mutation (whether a complete deletion or missense) determined the distribution of cancers and their burden, but beyond this, multiple renal tumours in individual patients did not converge onto the same trajectory. This observation suggests that following malignant transformation evolutionary contingency and chance dominate tumour evolution. Metastases from renal tumours were driven by loss of chromosomes 9p and 14q, reminiscent of sporadic renal tumours, suggesting that acquisition of metastatic competence is associated with a high degree of bottlenecking and highlighting these events as important targets for metastasis prevention.
Citation Format: Scott Shepherd, Alex Coulton, Cathy Vocke, Chris Ricketts, Marston Linehan, Samra Turajlic. The cell of origin is the dominant constraint in evolution of VHL related neoplasms [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA025.
Abstract PR011: Downregulation of the HIF2a target cyclin D1 underlies the efficacy of the HIF2a inhibitor belzutifan in kidney cancer
Authors: Shirole Nitin H. , Kesar Devishi , Sellers William R. , Kaelin William G. 
Published: August 2023

Abstract
Abstract: Most clear cell renal cell carcinomas (ccRCCs) are caused by loss of the pVHL tumor suppressor function. Inactivation of pVHL leads to increased accumulation of HIF2a, which drives ccRCC in preclinical models. HIF2a interacts with ARNT and functions as a heterodimeric transcription factor. HIF2a can activate hundreds of downstream target genes, including many that are suspected of playing a role in ccRCC pathogenesis based on their biological functions. Peloton Therapeutics developed a specific allosteric HIF2a inhibitor named PT2399, which disrupts the HIF2a-ARNT interaction and silences the HIF2a transcription program. Furthermore, PT2399 suppresses the growth of ccRCC cells in in-vitro and in-vivo assays. A more advanced version of PT2399, Belzutifan, was recently approved for treating tumors in patients with germline VHL mutations (VHL disease) and is in Phase 3 testing for sporadic ccRCCs. Since HIF2a is a transcriptional activator, we hypothesized that PT2399’s ability to suppress ccRCC is linked to repression of one or more HIF2a target genes. To identify these genes, we performed a pooled whole genome CRISPR activation (CRISPRa) screen in the presence or absence of PT2399. This screen identified multiple genes (“hits”) that, when activated, likely conferred resistance to PT2399. To further differentiate between direct vs indirect HIF2a targets that confer resistance to PT2399, we performed nascent RNA-seq (Pro-seq) after acute treatment of ccRCC cells with PT2399. Comparison of the CRISPRa and Pro-Seq data, together with secondary validation assays, identified CCND1, which encodes Cyclin D1, as a direct target gene of HIF2a that, when activated, confers complete resistance to PT2399 in multiple ccRCC cell lines. Additionally, we showed that wild-type Cyclin D1 (WT), but not a mutant (KE) that fails to activate CDK4/6, confers resistance to PT2399. Interestingly, Cyclin D1 overrides the growth inhibitory effect of PT2399 in ccRCC cells irrespective of pRB status. To identify the relevant Rb-independent substrates of Cyclin D1, we performed IP-MS experiments in RB1-/- ccRCC cells under substrate trapping conditions. Our preliminary data from these experiments suggests that RBL1 (p107) and RBL2 (p130) substitute for pRB in RB1-/- ccRCC cells. Our findings provide further support for CDK4/6 as a therapeutic target in ccRCC.
Citation Format: Nitin H. Shirole, Devishi Kesar, William R. Sellers, William G. Kaelin Jr. Downregulation of the HIF2a target cyclin D1 underlies the efficacy of the HIF2a inhibitor belzutifan in kidney cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr PR011.
Interações socioestatais: aspectos epistemológicos e contribuições a partir da Abordagem Estratégico-Relacional e da Perspectiva da Pólis
Authors: Marques Marcelo de Souza 
Published: August 2023

Recentemente, passou-se a observar a sedimentação de uma nova agenda de pesquisa no Brasil voltada às relações entre Estado e sociedade civil. Contra leituras essencialistas, fronteiriças e contextualistas, essa abordagem, denominada de interações socioestatais, tem assumido como perspectiva ontoepistemológica o argumento de que as esferas societária e institucional são fenômenos mutuamente constitutivos. Inserindo-se nessa agenda, objetiva-se avançar sobre as bases epistemológicas percebidas nos argumentos desse enfoque, destacando o pós-fundacionalismo, a contingência e ressaltando seu caráter relacional. Buscando novas contribuições, esses objetivos são explorados a partir da discussão de duas tradições intelectuais distintas, a Abordagem Estratégico-Relacional (AER) e a Perspectiva da Pólis (PP). Conclui-se que, quando lidas a partir dessas bases epistemológicas, ambas se complementam e informam elementos centrais para se pensar em termos de uma perspectiva de mútua constituição.
The Role of Multiscale Interaction in the Maintenance and Propagation of MJO in Boreal Winter
Authors: Ma Jiwang , Liang X. San , Chen Dake 
Published: August 2023

Abstract
The multiscale interaction and its role in the maintenance and propagation of the Madden–Julian oscillation (MJO) has been investigated using the newly developed multiscale window transform (MWT), the theory of canonical transfer, and the MWT-based multiscale energetics analysis (here particularly for this study, dry energetics analysis). The field variables are reconstructed/filtered with MWT onto three scale windows, namely a high-frequency window, intraseasonal window, and low-frequency window. Compositing the intraseasonal fields with respect to the real-time multivariate MJO (RMM) index unambiguously shows that the zonal extents of the easterlies and westerlies of MJO vary with the RMM phases, among which phases 4 and 2 are representative. In the former phase, the MJO has easterlies and westerlies within the same extent, while in the latter their extents are quite different. In phase 4, besides the previously discovered mechanisms such as pressure work and buoyancy conversion, the MJO is also energized by the canonical kinetic energy (KE) transfer from the low-frequency window to the intraseasonal window (signifying barotropic instability) on the west of its convection. But on the eastern side, MJO loses KE to the low-frequency window. The KE transport also functions like an energy sink. In phase 2, the MJO variabilities can be divided into an eastern part and a western part. The former is essentially the same as that in phase 4; for the latter, barotropic instability dominates. On the available potential energy (APE) budget, baroclinic instability and intraseasonal APE transport help produce and maintain the temperature anomalies. In contrast to previous energetics studies, our findings highlight the essential role played by multiscale interactions.
Understanding Broadcast Meteorologists’ Current and Future Use of Severe Weather Watches, Warnings, and Probabilistic Hazard Information
Authors: Obermeier Holly B. , Berry Kodi L. , Trujillo-Falcón Joseph E. 
Published: August 2023

Abstract
Broadcast meteorologists are essential in the communication of National Weather Service (NWS) warnings to the public. Therefore, it is imperative to include them in a user-centered approach for the design and implementation of new warning products. Forecasting a Continuum of Environmental Threats (FACETs) will modernize the way meteorologists forecast and communicate NWS warning information to the general public using rapidly updating probabilistic hazard information (PHI). Storm-scale PHI consists of probabilistic forecasts for severe wind/hail, tornadoes, and lightning hazards. Hence, NWS warnings would have the capacity to be supplemented by a quantitative or qualitative likelihood of hazard occurrence. The researchers conducting this study wanted to know what broadcast meteorologists thought about the inclusion of this likelihood information and how it could impact their decision-making and communication process. Using a nationwide survey, this team of researchers first asked broadcast meteorologists about their current practices for severe weather coverage using NWS watches and warnings. Next, broadcast meteorologists were introduced to multiple iterations of PHI prototypes and queried for their input. Findings indicated that broadcast meteorologists already face a complex decision-making and communication process under today’s warning paradigm. In addition, respondents were split on whether to explicitly communicate probabilities with their viewers. Respondents’ choices were also somewhat inconclusive regarding nomenclature, definitions of PHI and representations of PHI with warning polygons. These results suggest that PHI should feature user-driven, customizable options to fulfill broadcast meteorologists’ needs and that the iterative nature of the research-and-development process of PHI should continue.

Significance Statement
Broadcast meteorologists are vital communicators of dangerous weather to the public, leading researchers to study them more closely. Using a nationwide survey, this team of researchers wanted to know how broadcast meteorologists talk about tornadoes, large hail, and high winds to their viewers under today’s system of National Weather Service warnings. Survey findings indicated that broadcast meteorologists face a complex decision-making process when communicating dangerous weather. Any effort to modernize the current warning system, such as including hazard probability, should consider this complex process. Modernization should complement the role of broadcast meteorologists to ultimately serve the public and user-driven options should be a key component of any probabilistic information that is included in a future National Weather Service warning system.
Daily Sedative Interruption in Mechanically Ventilated Patients: Limited Data, Numerous Concerns
Authors: Bruno Jeffrey J. , Canada Todd W. 
Published: August 2023

Objective To review the literature regarding daily interruption of sedation in mechanically ventilated patients, the associated clinical outcomes, and the theoretical concerns that remain regarding such practice. Data Sources: A Medline search (1966 to February 2006) was performed using key search terms: critical illness, intensive care units, (analgesics, opioid), hypnotics and sedatives, (infusions, parenteral), drug administration schedule, and sedative interruption. References of identified manuscripts were also evaluated. Study Selection and Data Extraction All English-language articles identified from the data sources were evaluated and deemed relevant if they included an assessment of clinical outcomes. Data Synthesis Continuous IV infusion of analgesics and sedatives is commonly used in critically ill patients to help maintain a constant level of patient comfort. In mechanically ventilated patients, use of continuous IV sedation has been linked to a prolonged duration of mechanical ventilation, as well as a longer ICU and hospital length of stay (LOS). Daily sedative interruption has been shown to reduce the duration of mechanical ventilation, ICU LOS, and incidence of ICU-related complications without causing long-term (post-discharge) psychological sequelae. Although available data are limited, this information may be used to develop ICU sedation protocols in an attempt to minimize the incidence of oversedation and associated complications. Conclusion Daily interruption of continuous IV sedation may hold much promise for optimizing outcomes in the mechanically ventilated critically ill patient. However, theoretical concerns still remain including the practicality and safety of such practice.
Nutrition Support Pharmacist
Authors: Dickerson Roland N. 
Published: August 2023

Nutrition Support Pharmacist features issues pertinent to the practice of clinical pharmacy in the area of nutritional support. The column is edited by Dr. Roland Dickerson, Professor of Pharmacy, University of Tennessee Health Science Center; Memphis, TN. Address correspondence to Dr. Roland N. Dickerson, University of Tennessee Health Science Center, 26 South Dunlap St., Memphis, TN 38163. This article provides a summary of our approach to the management of acute hypocalcemia in critically ill patients receiving specialized nutrition support. It must be pointed out that there are other alternative effective approaches to managing this complication. Additionally, there are exceptions to the outlined treatment guidelines that the astute clinical must be able to identify. However, this approach will provide a sound foundation upon which to build your practice in the management of these difficult patients.
Study on Isocyanurate-Modified MDI. 1 — Preparation
Authors: Imai Yoshio , Hidai Takao , Inukai Takao , Nakanishi Takehisa 
Published: August 2023

Isocyanurate-modification of MDI was investigated. Certain modified MDIs which were stable liquids with lower viscosity were obtained. Direct trimerization of pure MDI resulted in crystallization at room temperature. After modification by diol with lower molecular weight, for instance tripropyleneglycol or tetrapropyleneglycol, at a molar ratio to isocyanate of more than 7·5/100, trimerization then produced a stable isocyanurate-modified isocyanate having an NCO content of about 25%. The trimerization of polymeric MDI by a tertiary amine catalyst, such as 2, 4, 6–tris(dimethylaminoethyl) phenol or N, N’, N”-tris(dimethylaminopropyl) hexahydro-s-triazine, followed by adding reaction-stopper and heating, also resulted in stable modified isocyanate with a 25 % NCO content.
Fire Properties of Isocyanate Based Rigid Foams
Authors: Wiedermann R. 
Published: August 2023

This paper deals with three different aspects of fire properties: (1) ignitability, (2) flame spread and (3) contribution to heat release. The results in different national fire tests of PU- and PIR-foams are discussed. It is found that results in some cases depend on the thickness and density of test samples. Comparison between small-scale and large-scale fire tests are made, the conclusion reached is that no correlation can be seen.