bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crustal Structure of the Western U.S. From Rayleigh and Love Wave Amplification Data
Authors: Sturgeon William , Ferreira Ana M. G. , Schardong Lewis , Marignier Augustin 
Published: August 2023

AbstractSurface wave amplification measurements have narrower depth sensitivity when compared to more traditional seismic observables such as surface wave dispersion measurements. In particular, Love wave amplification measurements have the advantage of strong sensitivity to the crust. For the first time, we explore the potential of Love wave amplification measurements to image crustal velocity in the western U.S. The effects of overtone interference, radial anisotropy and Moho depth are all explored. Consequently, we present SWUS‐crust, a three‐dimensional shear‐wave velocity model of crustal structure in the western U.S. We use Rayleigh wave amplification measurements in the period range of 38–114 s, along with Love wave amplification measurements in the period range of 38–62 s. We jointly invert over 6,400 multi‐frequency measurements using the Monte‐Carlo based Neighborhood Algorithm, which allows for uncertainty quantification. SWUS‐crust confirms several features observed in previous models, such as high‐velocity anomalies beneath the Columbia basin and low‐velocity anomalies beneath the Basin and Range province. Certain features are sharpened in our model, such as the northern border of the High‐Lava Plains in southern Oregon in the middle crust.
Full‐Depth Eddy Kinetic Energy in the Global Ocean Estimated From Altimeter and Argo Observations
Authors: Ni Qinbiao , Zhai Xiaoming , LaCasce J. H. , Chen Dake , Marshall David P. 
Published: August 2023

AbstractAlthough the surface eddy kinetic energy (EKE) has been well studied using satellite altimeter and surface drifter observations, our knowledge of EKE in the ocean interior is much more limited due to the sparsity of subsurface current measurements. Here we develop a new approach for estimating EKE over the full depth of the global ocean by combining 20 years of satellite altimeter and Argo float data to infer the vertical profile of eddies. The inferred eddy profiles are surface‐intensified at low latitudes and deep‐reaching at mid‐ and high latitudes. They compare favorably to the first empirical orthogonal function obtained from current meter velocities. The global‐integrated EKE estimated from the inferred profiles is about 3.1 × 1018 J, which is close to that estimated from the surface mode (3.0 × 1018 J) but about 30% smaller than that estimated from the traditional flat bottom modes (4.6 × 1018 J).
Impact of BMI on patient outcome in acute myeloid leukaemia patients receiving intensive induction therapy: a real-world registry experience
Authors: Enßle Julius C. , Wolf Sebastian , Scheich Sebastian , Weber Sarah , Kramer Michael , Ruhnke Leo , Schliemann Christoph , Mikesch Jan-Henrik , Krause Stefan , Sauer Tim , Hanoun Maher , Reinhardt Hans Christian , Kraus Sabrina , Kaufmann Martin , Hänel Mathias , Fransecky Lars , Burchert Andreas , Neubauer Andreas , Crysandt Martina , Jost Edgar , Niemann Dirk , Schäfer-Eckart Kerstin , Held Gerhard , Kaiser Ulrich , Wass Maxi , Schaich Markus , Müller-Tidow Carsten , Platzbecker Uwe , Baldus Claudia D. , Bornhäuser Martin , Röllig Christoph , Serve Hubert ,   Study Alliance Leukemia (SAL), Steffen Björn 
Published: August 2023

Abstract
Background
Acute myeloid leukaemia (AML) is treated with intensive induction chemotherapy (IT) in medically fit patients. In general, obesity was identified as a risk factor for all-cause mortality, and there is an ongoing debate on its impact on outcome and optimal dosing strategy in obese AML patients.

Methods
We conducted a registry study screening 7632 patients and assessed the impact of obesity in 1677 equally IT treated, newly diagnosed AML patients on the outcome (OS, EFS, CR1), comorbidities, toxicities and used dosing strategies.

Results
Obese patients (BMI ≥ 30) displayed a significant inferior median OS (29.44 vs. 47.94 months, P = 0.015) and CR1 rate (78.7% vs. 84.3%, P = 0.015) without differences in median EFS (7.8 vs. 9.89 months, P = 0.3) compared to non-obese patients (BMI < 30). The effect was predominantly observed in older (≥60 years) patients. Obesity was identified as an independent risk factor for death, and obese patients demonstrated higher rates of cardiovascular or metabolic comorbidities. No differences for OS, EFS, CR1 or treatment-related toxicities were observed by stratification according to used dosing strategy or dose reduction.

Conclusions
In conclusion, this study identifies obesity as an independent risk factor for worse OS in older AML patients undergoing curative IT most likely due to obesity-related comorbidities and not to dosing strategy.
Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis
Authors: del Puerto Ana , Lopez-Fonseca Coral , Simón-García Ana , Martí-Prado Beatriz , Barrios-Muñoz Ana L. , Pose-Utrilla Julia , López-Menéndez Celia , Alcover-Sanchez Berta , Cesca Fabrizia , Schiavo Giampietro , Campanero Miguel R. , Fariñas Isabel , Iglesias Teresa , Porlan Eva 
Published: August 2023

AbstractIn the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair.
Discovery of a pyrrole-pyridinimidazole derivative as novel SIRT6 inhibitor for sensitizing pancreatic cancer to gemcitabine
Authors: Song Nannan , Guan Xian , Zhang Siqi , Wang Yanqing , Wang Xuekai , Lu Zhongxia , Chong Daochen , Wang Jennifer Yiyang , Yu Rilei , Yu Wengong , Jiang Tao , Gu Yuchao 
Published: August 2023

AbstractPancreatic cancer is a highly aggressive cancer, and is primarily treated with gemcitabine, with increasing resistance. SIRT6 as a member of sirtuin family plays important roles in lifespan and diverse diseases, such as cancer, diabetes, inflammation and neurodegenerative diseases. Considering the role of SIRT6 in the cytoprotective effect, it might be a potential anticancer drug target, and is associated with resistance to anticancer therapy. However, very few SIRT6 inhibitors have been reported. Here, we reported the discovery of a pyrrole-pyridinimidazole derivative, 8a, as a new non-competitive SIRT6 inhibitor, and studied its roles and mechanisms in the antitumor activity and sensitization of pancreatic cancer to gemcitabine. Firstly, we found a potent SIRT6 inhibitor compound 8a by virtual screening and identified by molecular and cellular SIRT6 activity assays. 8a could effectively inhibit SIRT6 deacetylation activity with IC50 values of 7.46 ± 0.79 μM in FLUOR DE LYS assay, and 8a significantly increased the acetylation levels of H3 in cells. Then, we found that 8a could inhibit the cell proliferation and induce cell apoptosis in pancreatic cancer cells. We further demonstrate that 8a sensitize pancreatic cancer cells to gemcitabine via reversing the activation of PI3K/AKT/mTOR and ERK signaling pathways induced by gemcitabine and blocking the DNA damage repair pathway. Moreover, combination of 8a and gemcitabine induces cooperative antitumor activity in pancreatic cancer xenograft model in vivo. Overall, we demonstrate that 8a, a novel SIRT6 inhibitor, could be a promising potential drug candidate for pancreatic cancer treatment.
Targeting of SLC25A22 boosts the immunotherapeutic response in KRAS-mutant colorectal cancer
Authors: Zhou Qiming , Peng Yao , Ji Fenfen , Chen Huarong , Kang Wei , Chan Lam-Shing , Gou Hongyan , Lin Yufeng , Huang Pingmei , Chen Danyu , Wei Qinyao , Su Hao , Liang Cong , Zhang Xiang , Yu Jun , Wong Chi Chun 
Published: August 2023

AbstractKRAS is an important tumor intrinsic factor driving immune suppression in colorectal cancer (CRC). In this study, we demonstrate that SLC25A22 underlies mutant KRAS-induced immune suppression in CRC. In immunocompetent male mice and humanized male mice models, SLC25A22 knockout inhibits KRAS-mutant CRC tumor growth with reduced myeloid derived suppressor cells (MDSC) but increased CD8+ T-cells, implying the reversion of mutant KRAS-driven immunosuppression. Mechanistically, we find that SLC25A22 plays a central role in promoting asparagine, which binds and activates SRC phosphorylation. Asparagine-mediated SRC promotes ERK/ETS2 signaling, which drives CXCL1 transcription. Secreted CXCL1 functions as a chemoattractant for MDSC via CXCR2, leading to an immunosuppressive microenvironment. Targeting SLC25A22 or asparagine impairs KRAS-induced MDSC infiltration in CRC. Finally, we demonstrate that the targeting of SLC25A22 in combination with anti-PD1 therapy synergizes to inhibit MDSC and activate CD8+ T cells to suppress KRAS-mutant CRC growth in vivo. We thus identify a metabolic pathway that drives immunosuppression in KRAS-mutant CRC.
A flexible optoacoustic blood ‘stethoscope’ for noninvasive multiparametric cardiovascular monitoring
Authors: Jin Haoran , Zheng Zesheng , Cui Zequn , Jiang Ying , Chen Geng , Li Wenlong , Wang Zhimin , Wang Jilei , Yang Chuanshi , Song Weitao , Chen Xiaodong , Zheng Yuanjin 
Published: August 2023

AbstractQuantitative and multiparametric blood analysis is of great clinical importance in cardiovascular disease diagnosis. Although there are various methods to extract blood information, they often require invasive procedures, lack continuity, involve bulky instruments, or have complicated testing procedures. Flexible sensors can realize on-skin assessment of several vital signals, but generally exhibit limited function to monitor blood characteristics. Here, we report a flexible optoacoustic blood ‘stethoscope’ for noninvasive, multiparametric, and continuous cardiovascular monitoring, without requiring complicated procedures. The optoacoustic blood ‘stethoscope’ features the light delivery elements to illuminate blood and the piezoelectric acoustic elements to capture light-induced acoustic waves. We show that the optoacoustic blood ‘stethoscope’ can adhere to the skin for continuous and non-invasive in-situ monitoring of multiple cardiovascular biomarkers, including hypoxia, intravascular exogenous agent concentration decay, and hemodynamics, which can be further visualized with a tailored 3D algorithm. Demonstrations on both in-vivo animal trials and human subjects highlight the optoacoustic blood ‘stethoscope’‘s potential for cardiovascular disease diagnosis and prediction.
High-performance alkaline water electrolyzers based on Ru-perturbed Cu nanoplatelets cathode
Authors: Zuo Yong , Bellani Sebastiano , Ferri Michele , Saleh Gabriele , Shinde Dipak V. , Zappia Marilena Isabella , Brescia Rosaria , Prato Mirko , De Trizio Luca , Infante Ivan , Bonaccorso Francesco , Manna Liberato 
Published: August 2023

AbstractAlkaline electrolyzers generally produce hydrogen at current densities below 0.5 A/cm2. Here, we design a cost-effective and robust cathode, consisting of electrodeposited Ru nanoparticles (mass loading ~ 53 µg/cm2) on vertically oriented Cu nanoplatelet arrays grown on metallic meshes. Such cathode is coupled with an anode based on stacked stainless steel meshes, which outperform NiFe hydroxide catalysts. Our electrolyzers exhibit current densities as high as 1 A/cm2 at 1.69 V and 3.6 A/cm2 at 2 V, reaching the performances of proton-exchange membrane electrolyzers. Also, our electrolyzers stably operate in continuous (1 A/cm2 for over 300 h) and intermittent modes. A total production cost of US$2.09/kgH2 is foreseen for a 1 MW plant (30-year lifetime) based on the proposed electrode technology, meeting the worldwide targets (US$2–2.5/kgH2). Hence, the use of a small amount of Ru in cathodes (~0.04 gRu per kW) is a promising strategy to solve the dichotomy between the capital and operational expenditures of conventional alkaline electrolyzers for high-throughput operation, while facing the scarcity issues of Pt-group metals.
Harmonic to anharmonic tuning of moiré potential leading to unconventional Stark effect and giant dipolar repulsion in WS2/WSe2 heterobilayer
Authors: Chatterjee Suman , Dandu Medha , Dasika Pushkar , Biswas Rabindra , Das Sarthak , Watanabe Kenji , Taniguchi Takashi , Raghunathan Varun , Majumdar Kausik 
Published: August 2023

AbstractExcitonic states trapped in harmonic moiré wells of twisted heterobilayers is an intriguing testbed for exploring many-body physics. However, the moiré potential is primarily governed by the twist angle, and its dynamic tuning remains a challenge. Here we demonstrate anharmonic tuning of moiré potential in a WS2/WSe2 heterobilayer through gate voltage and optical power. A gate voltage can result in a local in-plane perturbing field with odd parity around the high-symmetry points. This allows us to simultaneously observe the first (linear) and second (parabolic) order Stark shift for the ground state and first excited state, respectively, of the moiré trapped exciton - an effect opposite to conventional quantum-confined Stark shift. Depending on the degree of confinement, these excitons exhibit up to twenty-fold gate-tunability in the lifetime (100 to 5 ns). Also, exciton localization dependent dipolar repulsion leads to an optical power-induced blueshift of ~ 1 meV/μW - a five-fold enhancement over previous reports.
The contribution of corporate initiatives to global renewable electricity deployment
Authors: Egli Florian , Zhang Rui , Hopo Victor , Schmidt Tobias , Steffen Bjarne 
Published: August 2023

AbstractClimate change is gaining importance on the agenda of senior decision makers in the private sector. Hence, corporate renewable electricity (RE) procurement may become more relevant to the energy transition. RE100 is the largest corporate initiative to foster RE procurement with 315 corporate members as of 2021. Yet, the contribution of such initiatives to the energy transition remains unclear, because public reporting is aggregated on the global level. Here, we develop an approach to map the electricity procured by RE100 companies to jurisdictions worldwide, which allows estimating whether and where RE100 can have a transformative impact. We find that these companies source electricity in 129 jurisdictions, accounting for <1% of total electricity generation (RE and non-RE), thus dampening the hopes about the impact of RE100 on the global energy transition. RE100 companies procure 1.4% of available RE, exceeding 20% in nine jurisdictions. To increase its impact, RE100 should focus on interim targets and expansion. By 2030, stringent and frequent interim targets could lead to a cumulated additional 361 TWh of RE procured by RE100 companies, and a realistic membership expansion could lead to procurement of 7.7% of globally available RE by RE100 companies.
A contracting Intertropical Convergence Zone during the Early Heinrich Stadial 1
Authors: Yang Yiping , Zhang Lanlan , Yi Liang , Zhong Fuchang , Lu Zhengyao , Wan Sui , Du Yan , Xiang Rong 
Published: August 2023

AbstractDespite the fact that the response of tropical hydroclimate to North Atlantic cooling events during the Heinrich Stadial 1 (HS1) has been extensively studied in African, South American and Indonesia, the nature of such responses remains debated. Here we investigate the tropical hydroclimate pattern over the Indo-Asian-Australian monsoon region during the HS1 by integrating hydroclimatic records, and examining a δ18Oseawater record from Globigerinoides ruber (white) in the tropical Indian Ocean. Our findings indicate that tropical hydrological conditions were synchronously arid in both hemispheres during the early HS1 (~18.3-16.3 ka) in the Indo-Asian-Australian monsoon region, except for a narrow, wet hydrological belt in northern low latitudes, suggesting the existence of a contracted tropical precipitation belt at that time. This study reveals that the meltwater discharge and resulting changes in global temperatures and El Niño exerted a profound influence on the tropical hydroclimate in the Indo-Asian-Australian monsoon region during the early HS1.
The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming
Authors: Saha Dhurjhoti , Hailu Solomon , Hada Arjan , Lee Junwoo , Luo Jie , Ranish Jeff A. , Lin Yuan-chi , Feola Kyle , Persinger Jim , Jain Abhinav , Liu Bin , Lu Yue , Sen Payel , Bartholomew Blaine 
Published: August 2023

AbstractThe SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome, controlling pluripotency and differentiation. Towards the C-terminus of the catalytic subunit of SWI/SNF is a motif called the AT-hook that is evolutionary conserved. The AT-hook is present in many chromatin modifiers and generally thought to help anchor them to DNA. We observe however that the AT-hook regulates the intrinsic DNA-stimulated ATPase activity aside from promoting SWI/SNF recruitment to DNA or nucleosomes by increasing the reaction velocity a factor of 13 with no accompanying change in substrate affinity (KM). The changes in ATP hydrolysis causes an equivalent change in nucleosome movement, confirming they are tightly coupled. The catalytic subunit’s AT-hook is required in vivo for SWI/SNF remodeling activity in yeast and mouse embryonic stem cells. The AT-hook in SWI/SNF is required for transcription regulation and activation of stage-specific enhancers critical in cell lineage priming. Similarly, growth assays suggest the AT-hook is required in yeast SWI/SNF for activation of genes involved in amino acid biosynthesis and metabolizing ethanol. Our findings highlight the importance of studying SWI/SNF attenuation versus eliminating the catalytic subunit or completely shutting down its enzymatic activity.
Membrane mediated mechanical stimuli produces distinct active-like states in the AT1 receptor
Authors: Poudel Bharat , Rajeshwar T Rajitha , Vanegas Juan M. 
Published: August 2023

AbstractThe Angiotensin II Type 1 (AT1) receptor is one of the most widely studied GPCRs within the context of biased signaling. While the AT1 receptor is activated by agonists such as the peptide AngII, it can also be activated by mechanical stimuli such as membrane stretch or shear in the absence of a ligand. Despite the importance of mechanical activation of the AT1 receptor in biological processes such as vasoconstriction, little is known about the structural changes induced by external physical stimuli mediated by the surrounding lipid membrane. Here, we present a systematic simulation study that characterizes the activation of the AT1 receptor under various membrane environments and mechanical stimuli. We show that stability of the active state is highly sensitive to membrane thickness and tension. Structural comparison of membrane-mediated vs. agonist-induced activation shows that the AT1 receptor has distinct active conformations. This is supported by multi-microsecond free energy calculations that show unique landscapes for the inactive and various active states. Our modeling results provide structural insights into the mechanical activation of the AT1 receptor and how it may produce different functional outcomes within the framework of biased agonism.
On the promise of personalized learning for educational equity
Authors: Dumont Hanna , Ready Douglas D. 
Published: August 2023

AbstractStudents enter school with a vast range of individual differences, resulting from the complex interplay between genetic dispositions and unequal environmental conditions. Schools thus face the challenge of organizing instruction and providing equal opportunities for students with diverse needs. Schools have traditionally managed student heterogeneity by sorting students both within and between schools according to their academic ability. However, empirical evidence suggests that such tracking approaches increase inequalities. In more recent years, driven largely by technological advances, there have been calls to embrace students’ individual differences in the classroom and to personalize students’ learning experiences. A central justification for personalized learning is its potential to improve educational equity. In this paper, we discuss whether and under which conditions personalized learning can indeed increase equity in K-12 education by bringing together empirical and theoretical insights from different fields, including the learning sciences, philosophy, psychology, and sociology. We distinguish between different conceptions of equity and argue that personalized learning is unlikely to result in “equality of outcomes” and, by definition, does not provide “equality of inputs”. However, if implemented in a high-quality way, personalized learning is in line with “adequacy” notions of equity, which aim to equip all students with the basic competencies to participate in society as active members and to live meaningful lives.
The co-delivery of adenovirus-based immune checkpoint vaccine elicits a potent anti-tumor effect in renal carcinoma
Authors: Jiang Nan , Zheng Yanyan , Ding Jiage , Wang Jiawei , Zhu Fei , Wang Meng , Sobhani Navid , Neeli Praveen , Wang Gang , Li Hailong , Zheng Junnian , Chai Dafei 
Published: August 2023

AbstractImmune-based checkpoint therapy has made significant progress in cancer treatment, but its therapeutic effect is limited. A replication-defective adenovirus (Ad) vaccine encoding tumor antigen carbonic anhydrase IX (CAIX) combined with Ad-encoding immune checkpoint PD-L1 was developed to treat renal carcinoma. Three tumor models, subcutaneous, lung metastasis and orthotopic tumor were established, and Ad vaccines were used to immunize them and evaluate the vaccine’s therapeutic effect. Compared to the single Ad vaccine group, the subcutaneous tumor growth was significantly reduced in Ad-CAIX/Ad-PD-L1 combination group. Co-immunization of Ad-CAIX/Ad-PD-L1 enhanced the induction and maturation of CD11c+ or CD8+CD11c+ DCs in the spleen and tumor and promoted the strong tumor-specific CD8+ T cell immune responses. In vivo CD8 T cell deletion assay showed that the anti-tumor effect of the Ad-CAIX/Ad-PD-L1 vaccine was mainly dependent on functional CD8+ T cell immune responses. Furthermore, the Ad-CAIX/Ad-PD-L1 vaccine effectively inhibited tumor growth and lung metastasis in metastatic or orthotopic models. These results indicate that the combination strategy of the immune checkpoint vaccine shows promising potential as an approach for malignant tumor therapy.