bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutrient Limitations Lead to a Reduced Magnitude of Disequilibrium in the Global Terrestrial Carbon Cycle
Authors: Wei Ning , Xia Jianyang , Wang Ying‐Ping , Zhang Xuanze , Zhou Jian , Bian Chenyu , Luo Yiqi 
Published: April 2022

AbstractThe terrestrial carbon (C) cycle is shifting to a state of dynamic disequilibrium under a rapid global climate change. However, the magnitude of such disequilibrium is inherently hard to measure directly. Abundant studies have revealed that the availability of nutrients, particularly nitrogen (N) and phosphorus (P), constrains ecosystem productivity and carbon stocks across the globe. However, whether and how nutrient limitation affects the disequilibrium magnitude of the terrestrial C cycle (Xp) has never been evaluated. Here, we developed an approach by combining a process‐based numerical model and an analytical framework to evaluate the role of nutrient limitation on Xp. We found that nutrient limitation did have significant impacts on the Xp. Over the modeled period of 1901–2013, absolute change in Xp was 497.6 PgC under the C‐only run, while it decreased to 155.6 and 124.3 PgC under N and NP limitations, respectively. To understand the underlying reasons, we further disaggregated the changes of Xp into changes in steady‐state C storage and transit C storage with the former being decomposed into a productivity‐driven change, an ecosystem‐C‐residence‐time‐driven (τE‐driven) change, and a change induced by productivity‐τE interactions. We found that nutrient constrained the increase in Xp primarily by dampening the productivity‐driven changes in the steady‐state C storage. Reductions in the productivity‐driven term under N and NP limitations accounted for 94.7% and 94.9%, respectively, of the reductions in the steady‐state C storage. These results indicate that nutrient limitations have profound impacts on future climate‐biosphere feedback by reducing the disequilibrium magnitude of the terrestrial C cycle.
Hydrodynamic metasurface for programming electromagnetic beam scanning on the Azimuth and elevation planes
Authors: Naqvi Aqeel Hussain , Lim Sungjoon 
Published: April 2022

AbstractThe development of multifunctional and reconfigurable metasurfaces capable of manipulating electromagnetic waves has created new opportunities for various exciting applications. Extensive efforts have been applied to exploiting active metasurfaces with properties that can be controlled by externally controlling active components. However, previous approaches have poor switch isolation, power handling limitations due to nonlinear effects, and complex biasing networks. Therefore, dynamically tunable metasurfaces have become a burgeoning field in many research areas. This paper reports a hydrodynamic metasurface (HMS) that can be programmed to realize electromagnetic beam scanning on the azimuth and elevation planes. The proposed HMS platform incorporates four micropumps, each controlling four metasurface elements via microfluidic channels, built into the HMS base. The proposed platform regulates microfluidic flow through micropumps, causing irregularities in incident wave transmission phase. An HMS was built as a proof of concept, and far-field scanning experiments were performed. Numerical and experimental results verify the feasibility of electromagnetic beam scanning using a hydrodynamic metasurface. This work advances metasurface research, with very high potential for wide-ranging application and a promising route for replacing bulky cascading active components.
A nanoforest-based humidity sensor for respiration monitoring
Authors: Chen Guidong , Guan Ruofei , Shi Meng , Dai Xin , Li Hongbo , Zhou Na , Chen Dapeng , Mao Haiyang 
Published: April 2022

AbstractTraditional humidity sensors for respiration monitoring applications have faced technical challenges, including low sensitivity, long recovery times, high parasitic capacitance and uncalibrated temperature drift. To overcome these problems, we present a triple-layer humidity sensor that comprises a nanoforest-based sensing capacitor, a thermistor, a microheater and a reference capacitor. When compared with traditional polyimide-based humidity sensors, this novel device has a sensitivity that is improved significantly by 8 times within a relative humidity range of 40–90%. Additionally, the integration of the microheater into the sensor can help to reduce its recovery time to 5 s. The use of the reference capacitor helps to eliminate parasitic capacitance, and the thermistor helps the sensor obtain a higher accuracy. These unique design aspects cause the sensor to have an excellent humidity sensing performance in respiration monitoring applications. Furthermore, through the adoption of machine learning algorithms, the sensor can distinguish different respiration states with an accuracy of 94%. Therefore, this humidity sensor design is expected to be used widely in both consumer electronics and intelligent medical instrument applications.
Behaviour change intervention for smokeless tobacco (ST) cessation delivered through dentists within a dental setting: a feasibility study protocol
Authors: Rasool Shaista , Holliday Richard , Khan Zohaib , Dobbie Fiona , Bauld Linda 
Published: April 2022

AbstractObjectives/AimTo adapt a structured behavioural support intervention for smokeless tobacco (ST) cessation and to assess the feasibility and acceptability of delivering the intervention via dentists within dental settings in Pakistan.Material and methodsThe study will have 3 phases: (1) Adapt a previously developed intervention to make it suitable for delivery in a clinical/dental setting through qualitative interviews with dental patients and dentists; (2) A multi-centre, pilot randomised control trial in two teaching dental hospitals in Pakistan. Participants (dental patients) will be randomly assigned to intervention or control group in a 1:1 allocation ratio to receive either a structured behavioural support intervention involving face to face counselling or self-help material plus usual care. Each participant will be in the study for approximately 6 months and the overall study is expected to run for 12 months; (3) An embedded qualitative process evaluation. All trial participants will be followed up at 3 and 6 months to assess self-reported ST use. Outcome measures will include: rates of eligibility, recruitment and retention, randomisation group cross-over rates, the provision of data on ST use behaviour, fidelity to the intervention and qualitative assessment of acceptability and feasibility.DiscussionDespite the high use of ST in Pakistan, users are offered negligible cessation support. The findings of this multi-centre, mixed-method feasibility study will inform the scope for a larger trial on ST cessation delivered through the existing dental health system.
Regorafenib inhibits epithelial-mesenchymal transition and suppresses cholangiocarcinoma metastasis via YAP1-AREG axis
Authors: Chang Yu-Chan , Li Chien-Hsiu , Chan Ming-Hsien , Chen Ming-Huang , Yeh Chun-Nan , Hsiao Michael 
Published: April 2022

AbstractCholangiocarcinoma (CCA) is a subtype of bile duct cancer usually diagnosed late with a low survival rate and no satisfactorily systemic treatment. Recently, regorafenib has been accepted as a second-line treatment for CCA patients. In this study, we investigated the potential signal transduction pathways mediated by regorafenib. We established a transcriptomic database for regorafenib-treated CCA cells using expression microarray chips. Our data indicate that regorafenib inhibits yes-associated protein 1 (YAP1) activity in various CCA cells. In addition, we demonstrated that YAP1 regulates epithelial-mesenchymal transition (EMT)-related genes, including E-cadherin and SNAI2. We further examined YAP1 activity, phosphorylation status, and expression levels of YAP1 downstream target genes in the regorafenib model. We found that regorafenib dramatically suppressed these events in CCA cells. Moreover, in vivo results revealed that regorafenib could significantly inhibit lung foci formation and tumorigenicity. Most importantly, regorafenib and amphiregulin (AREG) neutralize antibody exhibited synergistic effects against CCA cells. In a clinical setting, patients with high YAP1 and EMT expression had a worse survival rate than patients with low YAP1, and EMT expression did. In addition, we found that YAP1 upregulated the downstream target amphiregulin in CCA. Our findings suggest that AREG neutralizing antibody antibodies combined with regorafenib can reverse the CCA metastatic phenotype and EMT in vitro and in vivo. These findings provide novel therapeutic strategies to combat the metastasis of CCA.
Novel sarbecovirus bispecific neutralizing antibodies with exceptional breadth and potency against currently circulating SARS-CoV-2 variants and sarbecoviruses
Authors: Wang Yingdan , Liu Meiqin , Shen Yaping , Ma Yunping , Li Xiang , Zhang Yuanyuan , Liu Mei , Yang Xing-Lou , Chen Jun , Yan Renhong , Luan Die , Wang Yanqun , Chen Ying , Wang Qimin , Lin Haofeng , Li Yaning , Wu Kaiyue , Zhu Tongyu , Zhao Jincun , Lu Hongzhou , Wen Yumei , Jiang Shibo , Wu Fan , Zhou Qiang , Shi Zheng-Li , Huang Jinghe 
Published: April 2022

AbstractThe emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) has aroused concerns over their increased infectivity and transmissibility, as well as decreased sensitivity to SARS-CoV-2-neutralizing antibodies (NAbs) and the current coronavirus disease 2019 (COVID-19) vaccines. Such exigencies call for the development of pan-sarbecovirus vaccines or inhibitors to combat the circulating SARS-CoV-2 NAb-escape variants and other sarbecoviruses. In this study, we isolated a broadly NAb against sarbecoviruses named GW01 from a donor who recovered from COVID-19. Cryo-EM structure and competition assay revealed that GW01 targets a highly conserved epitope in a wide spectrum of different sarbecoviruses. However, we found that GW01, the well-known sarbecovirus NAb S309, and the potent SARS-CoV-2 NAbs CC12.1 and REGN10989 only neutralize about 90% of the 56 tested currently circulating variants of SARS-CoV-2 including Omicron. Therefore, to improve efficacy, we engineered an IgG-like bispecific antibody GW01-REGN10989 (G9) consisting of single-chain antibody fragments (scFv) of GW01 and REGN10989. We found that G9 could neutralize 100% of NAb-escape mutants (23 out of 23), including Omicron variant, with a geometric mean (GM) 50% inhibitory concentration of 8.8 ng/mL. G9 showed prophylactic and therapeutic effects against SARS-CoV-2 infection of both the lung and brain in hACE2-transgenic mice. Site-directed mutagenesis analyses revealed that GW01 and REGN10989 bind to the receptor-binding domain in different epitopes and from different directions. Since G9 targets the epitopes for both GW01 and REGN10989, it was effective against variants with resistance to GW01 or REGN10989 alone and other NAb-escape variants. Therefore, this novel bispecific antibody, G9, is a strong candidate for the treatment and prevention of infection by SARS-CoV-2, NAb-escape variants, and other sarbecoviruses that may cause future emerging or re-emerging coronavirus diseases.
Niche expansion and adaptive divergence in the global radiation of crows and ravens
Authors: Garcia-Porta Joan , Sol Daniel , Pennell Matt , Sayol Ferran , Kaliontzopoulou Antigoni , Botero Carlos A. 
Published: April 2022

AbstractThe processes that allow some lineages to diversify rapidly at a global scale remain poorly understood. Although earlier studies emphasized the importance of dispersal, global expansions expose populations to novel environments and may also require adaptation and diversification across new niches. In this study, we investigated the contributions of these processes to the global radiation of crows and ravens (genusCorvus). Combining a new phylogeny with comprehensive phenotypic and climatic data, we show thatCorvusexperienced a massive expansion of the climatic niche that was coupled with a substantial increase in the rates of species and phenotypic diversification. The initiation of these processes coincided with the evolution of traits that promoted dispersal and niche expansion. Our findings suggest that rapid global radiations may be better understood as processes in which high dispersal abilities synergise with traits that, like cognition, facilitate persistence in new environments.
Toward azo-linked covalent organic frameworks by developing linkage chemistry via linker exchange
Authors: Zhou Zhi-Bei , Tian Peng-Ju , Yao Jin , Lu Ya , Qi Qiao-Yan , Zhao Xin 
Published: April 2022

AbstractExploring new linkage chemistry for covalent organic frameworks (COFs) provides a strong driving force to promote the development of this emerging class of crystalline porous organic materials. Herein we report a strategy to synthesize COFs with azo linkage, one of the most important functional unit in materials science but having not yet been exploited as a linkage of COFs. This strategy is developed on the basis of in situ linker exchange, by which imine-linked COFs are completely transformed into azo-linked COFs (Azo-COFs). Moreover, distinct properties of Azo-COFs from their corresponding imine-linked precursors are observed, indicating unique property of Azo-COFs. This strategy provides a useful approach to develop new linkage chemistry for COFs. It also has established a synthetic method for azo-linked COFs, which not only enriches the family of COFs but also offers a platform to explore properties and applications of this class of crystalline porous conjugated polymers.
Lateral growth of cylinders
Authors: Sun Hui , Chen Shuai , Li Xiao , Leng Ying , Zhou Xiaoyan , Du Jianzhong 
Published: April 2022

AbstractThe precise control of the shape, size and microstructure of nanomaterials is of high interest in chemistry and material sciences. However, living lateral growth of cylinders is still very challenging. Herein, we propose a crystallization-driven fusion-induced particle assembly (CD-FIPA) strategy to prepare cylinders with growing diameters by the controlled fusion of spherical micelles self-assembled from an amphiphilic homopolymer. The spherical micelles are heated upon glass transition temperature (Tg) to break the metastable state to induce the aggregation and fusion of the amorphous micelles to form crystalline cylinders. With the addition of extra spherical micelles, these micelles can attach onto and fuse with the cylinders, showing the living character of the lateral growth of cylinders. Computer simulations and mathematical calculations are preformed to reveal the total energy changes of the nanostructures during the self-assembly and CD-FIPA process. Overall, we demonstrated a CD-FIPA concept for preparing cylinders with growing diameters.
PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration
Authors: Piao Wenji , Li Lushen , Saxena Vikas , Iyyathurai Jegan , Lakhan Ram , Zhang Yigang , Lape Isadora Tadeval , Paluskievicz Christina , Hippen Keli L. , Lee Young , Silverman Emma , Shirkey Marina W. , Riella Leonardo V. , Blazar Bruce R. , Bromberg Jonathan S. 
Published: April 2022

AbstractProgrammed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Little is known about their functions in T cell migration and there are contradictory data about their roles in regulatory T cell (Treg) function. Here we show activated Tregs and CD4 effector T cells (Teffs) use PD-1/PD-L1 and CD80/PD-L1, respectively, to regulate transendothelial migration across lymphatic endothelial cells (LECs). Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs. CD80/PD-L1 signaling up-regulates VCAM-1 through ERK and NFκB-p65. PD-1 and CD80 blockade reduces tumor egress of PD-1high fragile Tregs and Teffs into draining lymph nodes, respectively, and promotes tumor regression. These data provide roles for PD-L1 in cell migration and immune regulation.
R-loops at microRNA encoding loci promote co-transcriptional processing of pri-miRNAs in plants
Authors: Gonzalo Lucia , Tossolini Ileana , Gulanicz Tomasz , Cambiagno Damian A. , Kasprowicz-Maluski Anna , Smolinski Dariusz Jan , Mammarella María Florencia , Ariel Federico D. , Marquardt Sebastian , Szweykowska-Kulinska Zofia , Jarmolowski Artur , Manavella Pablo A. 
Published: April 2022

AbstractIn most organisms, the maturation of nascent RNAs is coupled to transcription. Unlike in animals, the RNA polymerase II (RNAPII) transcribes microRNA genes (MIRNAs) as long and structurally variable pri-miRNAs in plants. Current evidence suggests that the miRNA biogenesis complex assembly initiates early during the transcription of pri-miRNAs in plants. However, it is unknown whether miRNA processing occurs co-transcriptionally. Here, we used native elongating transcript sequencing data and imaging techniques to demonstrate that plant miRNA biogenesis occurs coupled to transcription. We found that the entire biogenesis occurs co-transcriptionally for pri-miRNAs processed from the loop of the hairpin but requires a second nucleoplasmic step for those processed from the base. Furthermore, we found that co- and post-transcriptional miRNA processing mechanisms co-exist for most miRNAs in a dynamic balance. Notably, we discovered that R-loops, formed near the transcription start site region of MIRNAs, promote co-transcriptional pri-miRNA processing. Furthermore, our results suggest the neofunctionalization of co-transcriptionally processed miRNAs, boosting countless regulatory scenarios.
Association of treatment-emergent symptoms identified by patient-reported outcomes with adjuvant endocrine therapy discontinuation
Authors: Smith Karen Lisa , Verma Neha , Blackford Amanda L. , Lehman Jennifer , Westbrook Kelly , Lim David , Fetting John , Wolff Antonio C. , Jelovac Daniela , Miller Robert S. , Connolly Roisin , Armstrong Deborah K. , Nunes Raquel , Visvanathan Kala , Riley Carol , Papathakis Katie , Zafman Nelli , Sheng Jennifer Y. , Snyder Claire , Stearns Vered 
Published: April 2022

AbstractMany patients discontinue endocrine therapy for breast cancer due to intolerance. Identification of patients at risk for discontinuation is challenging. The minimal important difference (MID) is the smallest change in a score on a patient-reported outcome (PRO) that is clinically significant. We evaluated the association between treatment-emergent symptoms detected by worsening PRO scores in units equal to the MID with discontinuation. We enrolled females with stage 0-III breast cancer initiating endocrine therapy in a prospective cohort. Participants completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance; Endocrine Subscale of the FACT-ES; and MOS-Sexual Problems (MOS-SP). We evaluated associations between continuous PRO scores in units corresponding to MIDs (PROMIS: 4-points; FACT-ES: 5-points; MOS-SP: 8-points) with time to endocrine therapy discontinuation using Cox proportional hazards models. Among 321 participants, 140 (43.6%) initiated tamoxifen and 181 (56.4%) initiated aromatase inhibitor (AI). The cumulative probability of discontinuation was 23% (95% CI 18–27%) at 48 months. For every 5- and 4-point worsening in endocrine symptoms and sleep disturbance respectively, participants were 13 and 14% more likely to discontinue endocrine therapy respectively (endocrine symptoms HR 1.13, 95% CI 1.02–1.25, p = 0.02; sleep disturbance HR 1.14, 95% CI 1.01–1.29,p = 0.03). AI treatment was associated with greater likelihood of discontinuation than tamoxifen. Treatment-emergent endocrine symptoms and sleep disturbance are associated with endocrine therapy discontinuation. Monitoring for worsening scores meeting or exceeding the MID on PROs may identify patients at risk for discontinuation.
Clinical relevance of pathogenic germline variants in mismatch repair genes in Chinese breast cancer patients
Authors: Hu Li , Sun Jie , Li Zhongwu , Qu Ziwei , Liu Yan , Wan Qiting , Liu Jiaming , Ding Xinyun , Zang Fan , Zhang Juan , Yao Lu , Xu Ye , Wang Yin , Xie Yuntao 
Published: April 2022

AbstractThe prevalence and clinical relevance of pathogenic germline variants in MMR genes have not been investigated in large series of breast cancers. In this study, we screened the germline variants in MMR genes in 8085 consecutive Chinese breast cancer patients, and investigated the MMR/PD-L1 protein expression and tumor mutation burden (TMB) of breast tumors from MMR variant carriers. We found that 15 of 8085 patients (0.19%) carried a pathogenic germline variant in MMR genes. Compared with non-carriers, MMR variant carriers might have worse recurrence-free survival (unadjusted hazard ratios [HR] = 2.70, 95% CI: 1.12–6.49, P = 0.027) and distant recurrence-free survival (unadjusted HR = 3.24, 95% CI: 1.45–7.22, P = 0.004). More importantly, some of the breast cancers from MMR carriers displayed MMR protein loss (5/13), TMB-high (2/10), and PD-L1 positive expression (9/13). This study showed that MMR variant carriers were rare in breast cancer. They might have worse survival and part of them might benefit from immunotherapy.
Unconventional dual 1D–2D quantum spin liquid revealed by ab initio studies on organic solids family
Authors: Ido Kota , Yoshimi Kazuyoshi , Misawa Takahiro , Imada Masatoshi 
Published: April 2022

AbstractOrganic solids host various electronic phases. Especially, a milestone compound of organic solid, $$\beta ^{\prime}$$

β

′

-X[Pd(dmit)2]2 with X=EtMe3Sb shows quantum spin-liquid (QSL) properties suggesting a novel state of matter. However, the nature of the QSL has been largely unknown. Here, we computationally study five compounds comprehensively with different X using 2D ab initio Hamiltonians and correctly reproduce the experimental phase diagram with antiferromagnetic order for X=Me4P, Me4As, Me4Sb, Et2Me2As and a QSL for X=EtMe3Sb without adjustable parameters. We find that the QSL for X=EtMe3Sb exhibits 1D nature characterized by algebraic decay of spin correlation along one direction, while exponential decay in the other direction, indicating dimensional reduction from 2D to 1D. The 1D nature indeed accounts for the experimental specific heat, thermal conductivity and magnetic susceptibility. The identified QSL, however, preserves 2D nature as well consistently with spin fractionalization into spinon with Dirac-like gapless excitations and reveals duality bridging the 1D and 2D QSLs.