bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA Therapeutics for Improving CAR T-cell Safety and Efficacy
Authors: Schaible Philipp , Bethge Wolfgang , Lengerke Claudia , Haraszti Reka Agnes 
Published: December 2022

Abstract
Autologous chimeric antigen receptor (CAR) T cells have recently emerged as potent tools in the fight against cancer, with promising therapeutic efficacy against hematological malignancies. However, several limitations hamper their widespread clinical use, including availability of target antigen, severe toxic effects, primary and secondary resistance, heterogeneous quality of autologous T cells, variable persistence, and low activity against solid tumors. Development of allogeneic off-the-shelf CAR T cells could help address some of these limitations but is impeded by alloimmunity with either rejection and limited expansion of allo-CAR T cells or CAR T cells versus host reactions. RNA therapeutics, such as small interfering RNAs, microRNAs, and antisense oligonucleotides, are able to silence transcripts in a sequence-specific and proliferation-sensitive way, which may offer a way to overcome some of the challenges facing CAR T-cell development and clinical utility. Here, we review how different RNA therapeutics or a combination of RNA therapeutics and genetic engineering could be harnessed to improve the safety and efficacy of autologous and allogeneic CAR T-cell therapy.
A Genetically Encoded Magnetic Resonance Imaging Reporter Enables Sensitive Detection and Tracking of Spontaneous Metastases in Deep Tissues
Authors: Nyström Nivin N. , McRae Sean W. , Martinez Francisco M. , Kelly John J. , Scholl Timothy J. , Ronald John A. 
Published: December 2022

AbstractMetastasis is the leading cause of cancer-related death. However, it remains a poorly understood aspect of cancer biology, and most preclinical cancer studies do not examine metastasis, focusing solely on the primary tumor. One major factor contributing to this paradox is a gap in available tools for accurate spatiotemporal measurements of metastatic spread in vivo. Here, our objective was to develop an imaging reporter system that offers sensitive three-dimensional (3D) detection of cancer cells at high resolutions in live mice. An organic anion-transporting polypeptide 1b3 (oatp1b3) was used as an MRI reporter gene, and its sensitivity was systematically optimized for in vivo tracking of viable cancer cells in a spontaneous metastasis model. Metastases with oatp1b3-MRI could be observed at the single lymph node level and tracked over time as cancer cells spread to multiple lymph nodes and different organ systems in individual animals. While initial single lesions were successfully imaged in parallel via bioluminescence, later metastases were largely obscured by light scatter from the initial node. Importantly, MRI could detect micrometastases in lung tissue comprised on the order of 1,000 cancer cells. In summary, oatp1b3-MRI enables longitudinal tracking of cancer cells with combined high resolution and high sensitivity that provides 3D spatial information and the surrounding anatomical context.Significance:An MRI reporter gene system optimized for tracking metastasis in deep tissues at high resolutions and able to detect spontaneous micrometastases in lungs of mice provides a useful tool for metastasis research.
Emerging Developments in ETS-Positive Prostate Cancer Therapy
Authors: Bowling Gartrell C. , Rands Mitchell G. , Dobi Albert , Eldhose Binil 
Published: December 2022

Abstract
Prostate cancer is a global health concern, which has a low survival rate in its advanced stages. Even though second-generation androgen receptor-axis inhibitors serve as the mainstay treatment options, utmost of the metastatic cases progress into castration-resistant prostate cancer after their initial treatment response with poor prognostic outcomes. Hence, there is a dire need to develop effective inhibitors that aim the causal oncogenes tangled in the prostate cancer initiation and progression. Molecular-targeted therapy against E-26 transformation-specific (ETS) transcription factors, particularly ETS-related gene, has gained wide attention as a potential treatment strategy. ETS rearrangements with the male hormone responsive transmembrane protease serine 2 promoter defines a significant number of prostate cancer cases and is responsible for cancer initiation and progression. Notably, inhibition of ETS activity has shown to reduce tumorigenesis, thus highlighting its potential as a clinical therapeutic target. In this review, we recapitulate the various targeted drug approaches, including small molecules, peptidomimetics, nucleic acids, and many others, aimed to suppress ETS activity. Several inhibitors have demonstrated ERG antagonist activity in prostate cancer, but further investigations into their molecular mechanisms and impacts on nontumor ETS-containing tissues is warranted.
NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations
Authors: Drilon Alexander , Horan Joshua C. , Tangpeerachaikul Anupong , Besse Benjamin , Ou Sai-Hong Ignatius , Gadgeel Shirish M. , Camidge D. Ross , van der Wekken Anthonie J. , Nguyen-Phuong Linh , Acker Adam , Keddy Clare , Nicholson Katelyn S. , Yoda Satoshi , Mente Scot , Sun Yuting , Soglia John R. , Kohl Nancy E. , Porter James R. , Shair Matthew D. , Zhu Viola , Davare Monika A. , Hata Aaron N. , Pelish Henry E. , Lin Jessica J. 
Published: December 2022

AbstractROS1 tyrosine kinase inhibitors (TKI) have been approved (crizotinib and entrectinib) or explored (lorlatinib, taletrectinib, and repotrectinib) for the treatment of ROS1 fusion–positive cancers, although none of them simultaneously address the need for broad resistance coverage, avoidance of clinically dose-limiting TRK inhibition, and brain penetration. NVL-520 is a rationally designed macrocycle with &gt;50-fold ROS1 selectivity over 98% of the kinome tested. It is active in vitro against diverse ROS1 fusions and resistance mutations and exhibits 10- to 1,000-fold improved potency for the ROS1 G2032R solvent-front mutation over crizotinib, entrectinib, lorlatinib, taletrectinib, and repotrectinib. In vivo, it induces tumor regression in G2032R-inclusive intracranial and patient-derived xenograft models. Importantly, NVL-520 has an ∼100-fold increased potency for ROS1 and ROS1 G2032R over TRK. As a clinical proof of concept, NVL-520 elicited objective tumor responses in three patients with TKI-refractory ROS1 fusion–positive lung cancers, including two with ROS1 G2032R and one with intracranial metastases, with no observed neurologic toxicities.Significance:The combined preclinical features of NVL-520 that include potent targeting of ROS1 and diverse ROS1 resistance mutations, high selectivity for ROS1 G2032R over TRK, and brain penetration mark the development of a distinct ROS1 TKI with the potential to surpass the limitations of earlier-generation TKIs for ROS1 fusion–positive patients.This article is highlighted in the In This Issue feature, p. 517
Inferring the Properties of Snow in Southern Ocean Shallow Convection and Frontal Systems Using Dual-Polarization C-Band Radar
Authors: Mace Gerald G. , Protat Alain , Benson Sally , McGlynn Paul 
Published: December 2022

Abstract
We use dual-polarization C-band data collected in the Southern Ocean to examine the properties of snow observed during a voyage in the austral summer of 2018. Using existing forward modeling formalisms based on an assumption of Rayleigh scattering by soft spheroids, an optimal estimation algorithm is implemented to infer snow properties from horizontally polarized radar reflectivity, the differential radar reflectivity, and the specific differential phase. From the dual-polarization observables, we estimate ice water content qi, the mass-mean particle size Dm, and the exponent of the mass–dimensional relationship bm that, with several assumptions, allow for evaluation of snow bulk density, and snow number concentration. Upon evaluating the uncertainties associated with measurement and forward model errors, we determine that the algorithm can retrieve qi, Dm, and bm within single-pixel uncertainties conservatively estimated in the range 120%, 60%, and 40%, respectively. Applying the algorithm to open-cellular convection in the Southern Ocean, we find evidence for secondary ice formation processes within multicellular complexes. In stratiform precipitation systems we find snow properties and infer processes that are distinctly different from the shallow convective systems with evidence for riming and aggregation being common. We also find that embedded convection within the frontal system produces precipitation properties consistent with graupel. Examining 5 weeks of data, we show that snow in open-cellular cumulus has higher overall bulk density than snow in stratiform precipitation systems with implications for interpreting measurements from space-based active remote sensors.
On the Existence of Low-Dimensional Chaos of the Tropical Cyclone Intensity in an Idealized Axisymmetric Simulation
Authors: Kieu Chanh , Cai Weiran , Fan Wai-Tong (Louis) 
Published: December 2022

Abstract
This study examines the potential limit in predicting tropical cyclone (TC) intensity under idealized conditions. Using the phase-space reconstruction method for TC intensity time series obtained from the CM1 idealized simulations, it is found that CM1 axisymmetric dynamics contain low-dimensional chaos at the maximum intensity equilibrium. Examination of several attractor invariants including the largest Lyapunov exponent, the Sugihara–May correlation, and the correlation dimension captures a consistent range of the chaotic attractor dimension between 4 and 5 for TC intensity at the maximum intensity equilibrium. In addition, the intensity error doubling time estimated from the largest Lyapunov exponent is roughly 1–3 h, which accords with the decay time obtained from the Sugihara–May correlation. Furthermore, the findings in this study reveal a relatively short TC intensity predictability limit for CM1, which is ∼3–9 h based on the maximum tangential wind but noticeably longer for the minimum central pressure (∼12–18 h) after reaching the mature stage. So long as the traditional metrics for TC intensity such as the maximum surface wind or the minimum central pressure is used for intensity forecast, our results support that TC intensity forecast errors will not be reduced indefinitely in any model, even in the absence of all model and observational errors. As such, the future improvement of TC intensity forecast should be based on different metrics beyond the absolute intensity errors that are currently used in real-time intensity verification.

Significance Statement
Using the phase-space reconstruction method for tropical cyclone (TC) intensity time series obtained from idealized axisymmetric simulations, we show that TC axisymmetric dynamics in CM1 possesses low-dimensional chaos at the maximum intensity equilibrium. This low-dimensional dynamics explains the long tradition of representing TC intensity by a few measures as in the current practice. The chaotic property of CM1 axisymmetric dynamics also suggests a relatively short predictability range for TC intensity at the maximum intensity equilibrium. The potential existence of low-dimensional chaos for TC intensity in CM1 idealized simulations as found in this study supports the use of different intensity verification metrics beyond the traditional absolute intensity errors currently used in operational model evaluation.
Link between the Land–Sea Thermal Contrast and the Asian Summer Monsoon
Authors: Zuo Zhiyan , Zhang Kaiwen 
Published: December 2022

Abstract
The land–sea thermal contrast is the foundation of the occurrences of the Asian summer monsoon (ASM). Using multiobservational datasets and model simulations covering the period 1960–2018, this study investigates the relationship that links the thermal contrast between the Asian landmass and the Indian Ocean (TCAI) to the ASM and evaluates the effects of the various driving factors that influence the TCAI in the climate models. The tropospheric TCAI is highly consistent with the ASM circulation, with a stronger ASM circulation and larger tropospheric TCAI before the 1970s and after the late 1990s than those seen from the 1970s to the late 1990s. The tropospheric TCAI is also closely related to rainfall over the Indian landmass and the south-flood–north-drought pattern over eastern China. Thus, the tropospheric TCAI reliably reflects the state of the ASM system and could be used as a new ASM index that directly describes the land–sea thermal contrast. The variation of the surface TCAI is highly consistent with that of the tropospheric TCAI. The model simulation suggests that the main drivers of the surface TCAI are anthropogenic forcing and the Atlantic multidecadal oscillation (AMO). Anthropogenic forcing dominates SAT variations over the Indian Ocean, whereas the AMO plays a major role in SAT variations over the Asian landmass, which introduces a large uncertainty into the projections of the ASM.
Impact of Synoptic Wind Intensification and Relaxation on the Dynamics and Heat Budget of the South Senegalese Upwelling Sector
Authors: Chabert Pierre , Capet Xavier , Echevin Vincent , Lazar Alban , Hourdin Christophe , Ndoye Siny 
Published: December 2022

Abstract
In addition to their well-known seasonal cycle, eastern boundary upwelling systems (EBUS) undergo modulation on shorter synoptic to intraseasonal time scales. Energetic intensifications and relaxations of upwelling-favorable winds with 5–10-day typical time scales can impact the EBUS dynamics and biogeochemical functioning. In this work the dynamical effects of wind-forced synoptic fluctuations on the South Senegalese Upwelling Sector (SSUS) are characterized. The region geomorphology is unique with its wide continental shelf and a major coastline discontinuity at its northern edge. The ocean response to synoptic events is explored using a modeling framework that involves applying idealized synoptic wind intensification or relaxation to a five-member climatological SSUS ensemble run. Model evaluation against sparse midshelf in situ observations indicates qualitative agreement in terms of synoptic variability of temperature, stratification, and ocean currents, despite a moderate but systematic bias in current intensity. Modeled synoptic wind and heat flux fluctuations produce clear modulations of all dynamical variables with robust SSUS-scale and mesoscale spatial patterns. A mixed layer heat budget analysis is performed over the continental shelf to uncover the dominant processes involved in SSUS synoptic variability. Modulations of horizontal advection and atmospheric forcing are the leading-order drivers of heat changes during either wind intensification or relaxation while vertical dynamics is of primary importance only in a very localized area. Also, modest asymmetries in the oceanic responses to upwelling intensification and relaxation are only identified for meridional velocities. This brings partial support to the hypothesis that synoptic variability has a modest net effect on the climatological state and functioning of upwelling systems dynamics.
Social anxiety and depression symptoms in Chinese left-behind children after the lifting of COVID-19 lockdown: A network analysis
Authors: Li Kuiliang , Ren Lei , Zhang Lei , Liu Chang , Zhao Mengxue , Zhan Xiaoqing , Li Ling , Luo Xi , Feng Zhengzhi 
Published: December 2022

Background:Returning to social life after the lifting of COVID-19 lockdown may increase risk of social anxiety, which is highly co-morbid with depression. However, few studies have reported the association between them.Aims:To explore the complex relationship between social anxiety and depression symptoms in left-behind children after the lifting of the COVID-19 lockdown.Methods:A cross-sectional survey was conducted 6 months after the lockdown removal. A total of 3,107 left-behind children completed the survey with a mean age of 13.33 and a response rate of 87.77%. Depression and social anxiety severity were assessed by the DSM-5 Patient Health Questionnaire for Adolescents and the DSM-5 Social Anxiety Disorder Questionnaire, respectively. The symptom-level association between the two disorders was examined using network analysis.Results:After the lifting of COVID-19 lockdown, the prevalence of depression and social anxiety in left-behind children was 19.57% and 12.36%, respectively, with a co-morbidity rate of 8.98%. Network analysis showed that “Social tension” and “Social avoidance” had the greatest expected influence; “Humiliation” and “Motor” were bridge symptom nodes in the network. The directed acyclic graph indicated that “Social fright” was at the upstream of all symptoms.Conclusion:Attention should be paid to social anxiety symptoms in left-behind children after the lifting of COVID-19 lockdown. Prevention and intervention measures should be taken promptly to reduce the comorbidity of social anxiety and depression symptoms in the left-behind children after the lifting of lockdown.
An Objective Structured Laboratory Animal Science Examination (OSLASE) to ensure researchers’ professional competence in laboratory animal science
Authors: Costa Andreia , Lamas Sofia , Correia Maria Rui , Gomes Maria S , Costa Manuel J , Olsson I Anna S 
Published: December 2022

The evaluation of the competence of personnel working with laboratory animals is currently a challenge. Directive 2010/63/EU establishes that staff must have demonstrated competence before they perform unsupervised work with living animals. Nevertheless, there is a lack of research into education and training in laboratory animal science, and the establishment of assessment strategies to confirm researchers’ competence remains largely unaddressed. In this study, we analysed the implementation of a practical assessment strategy over three consecutive years (2018–2021) using the Objective Structured Laboratory Animal Science Exam (OSLASE) developed previously by us to assess professional competence. The interrater reliability (IRR) was determined based on the assessors’ rating of candidates’ performance at different OSLASE stations using weighted kappa (Kw) and percentage of agreement. Focus group interviews were conducted to access trainees’ acceptability regarding the OSLASE. There was a moderate-to-good Kw for the majority of the scales’ items (0.79 ± 0.20 ≤ Kw ≥ 0.45 ± 0.13). The percentages of agreement were also acceptable (≥75%) for all scale items but one. Trainees reported that the OSLASE had a positive impact on their engagement during practical training, and that it clarified the standards established for their performance and the skills that required improvement. These preliminary results illustrate how assessment strategies, such as the OSLASE, can be implemented in a manner that is useful for both assessors and trainees. Examen structuré objectif de science animale de laboratoire (OSASSE) pour assurer la compétence professionnelle des chercheurs en SAL
Searching for the Informal Labor Movement: Theorizing Class and Collective Action among Informal Workers in West Africa
Authors: McDermott Joshua Lew 
Published: December 2022

Amid renewed debates and theorizing about informality and the role of informal workers in Africa and across the globe, there remains little in the way of class-based understandings of Africa's informal workers and of informal worker politics. Marxists, especially Analytical Marxists, have been slow to study and consider the role and potential role of informal workers in geopolitics and class struggle across the Global South, and Africa, in particular. Drawing on ethnographic field work and interviews conducted in Sierra Leone, and broader informal worker-led struggles and events across Africa and the Global South, this work argues for a renewed understanding of collective action and class formation among informal workers. JEL Classification: J0, J2, J6
Effect of electrochemical oxidation degree of carbon fiber on the interfacial properties of carbon fiber–reinforced polyaryletherketone composites
Authors: Gao Dongting , Yang Hongru , Liu Gang , Chen Chunhai , Yao Jianan , Li Chang 
Published: December 2022

Electrochemical oxidation of carbon fiber (CF) is used to enhance the interfacial adhesion of CF-reinforced polyaryletherketone (CF/PAEK) composites. The effect of current intensity parameter on surface structure of CF and interfacial properties of the corresponding thermoplastic composites are deeply investigated. The results show that the current intensity in the range of 80 A–300 A does not lead to a decrease in the mechanical property of CFs. When the current intensity is 200 A, CF/PAEK composites have the highest interfacial performance, which is mainly due to the improvement of CF surface roughness, wettability, and oxygen content. In addition, the degree of graphitization of CF surface is also a crucial factor affecting the interfacial properties of CF/PAEK. The higher the content of carboxyl groups, the more disordered the structures exist on the CF surface, which are not conducive to the strong adhesion of CF to PAEK resin. Therefore, balancing the wettability and graphitization degree of the CF surface is the key to enhancing the CF/PAEK interfacial properties by electrochemical treatment techniques.
Understanding COVID-19 Risk Perceptions and Precautionary Behaviors in Black Chicagoans: A Grounded Theory Approach
Authors: Chebli Perla , McBryde-Redzovic Aminah , Al-Amin Nadia , Gutierrez-Kapheim Melissa , Molina Yamilé , Mitchell Uchechi A. 
Published: December 2022

Objectives To determine whether actual community-level risk for COVID-19 in the Black community influenced individual perceptions of community-level and personal risk and how self-assessment of personal risk was reflected in the adoption of COVID-19 precautionary behaviors. Methods Semistructured interviews were conducted with 20 Black Chicago adults from February to July 2021. A grounded theory approach was used for the qualitative analysis and initial, focused, and theoretical coding were performed. Results We developed a grounded model consisting of four major themes: (a) Pre-Existing Health Conditions; (b) Presence of COVID-19 Infection in Participant Social Network; (c) COVID-19-Related Information, Participant Trust, and Perceived Personal Risk; and (d) Perceived Higher Burden of COVID-19 in the Black Community. Conclusions Higher perceptions of personal risk were shaped by pre-existing health conditions and experiences with COVID-19 in one’s social network but were not influenced by perceived higher burden of COVID-19 in the Black community. Policy Implications Black adults’ perceptions of their individual risk and precautionary behaviors were not congruent with public health data and recommendations. Therefore, COVID-19 messaging and mitigation should be informed by local community engagement and transparent communication.