bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prevalence and Implications of Gender Blindness in Quantitative Political Science Research
Authors: Forman-Rabinovici Aliza , Mandel Hadas
Published: July 2022

The topic of gender blindness is increasingly gaining the attention of researchers. Even in fields that do not commonly engage with gender, gender blindness has been recognized as a factor that has potential to limit the validity of research findings. This article explores the prevalence and implications of gender blindness in quantitative research for political science outcomes. We first reanalyze three articles recently published in the American Journal of Political Science (AJPS) to illustrate the impact of gender blindness on quantitative research. Next, we classify all articles with quantitative methodology published in the AJPS in 2018 and 2019 by the degree of gender blindness in the research design. Our findings demonstrate how gender blindness impacts outcomes and estimate its prevalence in political science. They show that accounting for gender yields more accurate results and facilitates a better understanding of political behavior and phenomena.
Markets, repugnance, and externalities
Authors: Krawiec Kimberly D.
Published: July 2022

This Article considers one aspect of the ongoing debate about the moral limits of markets – namely, the purported harmful effects of market transactions on particular relations, goods, services, or society at large, due to an inappropriate valuation. In other words, the argument is that some markets are ‘repugnant’ because they degrade and corrupt a variety of nonmarket values and relations, not just to the willing parties to the exchange, but to larger segments of society. This objection contains both a (frequently unacknowledged) empirical component and a moral component. This Article critiques these empirical claims on two grounds. First, market skeptics fail to provide evidence of the negative effects they hypothesize, despite widespread variation over time and across legal regimes. Second, these objections fail to account for the well-documented human tendency to fashion repugnant exchanges in a manner that reinforces – rather than undermines – deeply held values and relationships.
Looking Forward Through and Beyond the Western Classics of International Law
Authors: DE LA RASILLA Ignacio
Published: July 2022

The study of the Western classics of international law with Francisco de Vitoria and Hugo Grotius at its core is the foundational stone on which the whole edifice of today's ever-expanding history of international law was built upon. The article provides a gateway to Vitoria and Grotius's significance for international law and its history by providing a tenfold list of attributes of what makes a classic of international law. It then examines the rise to pre-eminence of the study of the classics of international law and surveys the main methodological responses addressed to correcting the historiographical blind spots and large gaps in legal history that the privileging of these Western “great men” have triggered. The conclusion recaps the importance of looking forward through, but also beyond, the deeply West-centric and male-dominated intellectual canon of international law in an international order the centre of gravity of which is inexorably moving eastwards.
Variable Phase Relationship Between Monsoon and Temperature in East Asia During Termination II Revealed by Oxygen and Clumped Isotopes of a Northern Chinese Stalagmite
Authors: Duan Wuhui , Wang Xu , Tan Ming , Cui Linlin , Wang Xuefeng , Xiao Zhengyi
Published: July 2022

Termination II (T‐II) is a natural reference for evaluating the potential effect of substantial ice sheets melting on monsoon and temperature changes caused by global warming. However, the phase relationship of East Asian summer monsoon (EASM) and temperature during T‐II remains enigmatic due to the lack of paleotemperature proxies. Here, we provide high‐resolution mean annual atmospheric temperature (MAAT) estimates during T‐II in northern China using speleothem clumped isotopes. Compared with present, the maximum MAAT at the last interglacial was 1.8 ± 1.5°C higher, and the minimum MAAT at the penultimate glaciation was 6.8 ± 1.3°C lower. EASM and temperature decoupled during the first 2100 years of the record and coupled onwards. This variable phase relationship is plausibly modified by the strength of the cold anomaly in North Atlantic triggered by collapse of ice sheets. When the cold anomaly exceeds a boundary condition, it could not only weaken EASM but also lower temperature.
Analysis of the Configuration Relationship Between the Morphological Characteristics of Lightning Channels and the Charge Structure Based on the Localization of VHF Radiation Sources
Authors: Li YuRui , Zhang Yang , Zhang YiJun , Krehbiel Paul R.
Published: July 2022

The lightning channel morphology is closely related to developmental processes, which depends on the charge structure. There is currently a lack of understanding of how lightning channel morphology reveals developmental characteristics and charge structure. Based on the Lightning mapping array radiation source localization data of six lightning flashes, we studied the lightning channel morphology characterization method and obtained the spatial distribution of the fractal dimension (FD). We found that the fractal distribution had a consistent spatial and temporal correspondence with the channel development characteristics. Compared to regions with unidirectional extended channels, regions with more channel branches or direction change of channel development have a larger FD and a higher power density, where horizontal channel development is accelerated. These correspondence features reflect the inhomogeneous presence of pocket charge, which provides a new method to use lightning morphology information to reveal the characteristics of charge level distribution within thunderstorm clouds.
Satellite‐Observed Vegetation Responses to Intraseasonal Precipitation Variability
Authors: Harris Bethan L. , Taylor Christopher M. , Weedon Graham P. , Talib Joshua , Dorigo Wouter , van der Schalie Robin
Published: July 2022

There is limited understanding of how vegetation responds to intraseasonal modes of rainfall variability despite their importance in many tropical regions. We use observations of precipitation and X‐band Vegetation Optical Depth (VOD) from 2000 to 2018 to assess the relationships between rainfall and vegetation water content on 25–60‐day timescales. Cross‐spectral analysis identifies coherent intraseasonal relationships between precipitation and VOD, mostly in arid or semi‐arid regions where vegetation is water‐limited. Changes in VOD tend to lag anomalous rainfall, usually within 7 days. The fastest vegetation response is observed in sparsely vegetated areas (median 3 days). Following strong intraseasonal wet events, anomalously high VOD can persist for 2 months after the rainfall peak. This vegetation response can feed back onto the atmosphere, so improved representation of vegetation responses in models has the potential to improve subseasonal‐to‐seasonal forecasts.
The interaction of early life factors and depression-associated loci affecting the age at onset of the depression
Authors: Chen Yujing , Pan Chuyu , Cheng Shiqiang , Li Chun’e , Zhang Huijie , Zhang Zhen , Zhang Jingxi , Yao Yao , Meng Peilin , Yang Xuena , Liu Li , Cheng Bolun , Jia Yumeng , Wen Yan , Zhang Feng
Published: July 2022

Multiple previous studies explored the associations between early life factors and the age at onset of the depression. However, they only focused on the influence of environmental or genetic factors, without considering the interactions between them. Based on previous genome-wide association study (GWAS) data, we first calculated polygenic risk score (PRS) for depression. Regression analyses were conducted to assess the interacting effects of depression PRS and 5 early life factors, including felt hated by family member (N = 40,112), physically abused by family (N = 40,464), felt loved (N = 35633), and sexually molested (N = 41,595) in childhood and maternal smoking during pregnancy (N = 38,309), on the age at onset of the depression. Genome-wide environment interaction studies (GWEIS) were then performed to identify the genes interacting with early life factors for the age at onset of the depression. In regression analyses, we observed significant interacting effects of felt loved as a child and depression PRS on the age at onset of depression in total sample (β = 0.708, P = 5.03 × 10−3) and males (β = 1.421, P = 7.64 × 10−4). GWEIS identified a novel candidate loci interacting with felt loved as a child at GSAP (rs2068031, P = 4.24 × 10–8) and detected several genes with suggestive significance association, such as CMYA5 (rs7343, P = 2.03 × 10–6) and KIRREL3 (rs535603, P = 4.84 × 10–6) in males. Our results indicate emotional care in childhood may affect the age at onset of depression, especially in males, and GSAP plays an important role in their interaction.
Enhanced top-down sensorimotor processing in somatic anxiety
Authors: Bouziane Ismail , Das Moumita , Friston Karl J. , Caballero-Gaudes Cesar , Ray Dipanjan
Published: July 2022

Functional neuroimaging research on anxiety has traditionally focused on brain networks associated with the psychological aspects of anxiety. Here, instead, we target the somatic aspects of anxiety. Motivated by the growing appreciation that top-down cortical processing plays a crucial role in perception and action, we used resting-state functional MRI data from the Human Connectome Project and Dynamic Causal Modeling (DCM) to characterize effective connectivity among hierarchically organized regions in the exteroceptive, interoceptive, and motor cortices. In people with high (fear-related) somatic arousal, top-down effective connectivity was enhanced in all three networks: an observation that corroborates well with the phenomenology of anxiety. The anxiety-associated changes in connectivity were sufficiently reliable to predict whether a new participant has mild or severe somatic anxiety. Interestingly, the increase in top-down connections to sensorimotor cortex were not associated with fear affect scores, thus establishing the (relative) dissociation between somatic and cognitive dimensions of anxiety. Overall, enhanced top-down effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of trait somatic anxiety.
Beyond controlling cell size: functional analyses of S6K in tumorigenesis
Authors: Wu Xueji , Xie Wei , Xie Wenxuan , Wei Wenyi , Guo Jianping
Published: July 2022

As a substrate and major effector of the mammalian target of rapamycin complex 1 (mTORC1), the biological functions of ribosomal protein S6 kinase (S6K) have been canonically assigned for cell size control by facilitating mRNA transcription, splicing, and protein synthesis. However, accumulating evidence implies that diverse stimuli and upstream regulators modulate S6K kinase activity, leading to the activation of a plethora of downstream substrates for distinct pathobiological functions. Beyond controlling cell size, S6K simultaneously plays crucial roles in directing cell apoptosis, metabolism, and feedback regulation of its upstream signals. Thus, we comprehensively summarize the emerging upstream regulators, downstream substrates, mouse models, clinical relevance, and candidate inhibitors for S6K and shed light on S6K as a potential therapeutic target for cancers.
Activation of the JNKs/ATM-p53 axis is indispensable for the cytoprotection of dermal fibroblasts exposed to UVB radiation
Authors: Mavrogonatou Eleni , Angelopoulou Maria , Rizou Sophia V. , Pratsinis Harris , Gorgoulis Vassilis G. , Kletsas Dimitris
Published: July 2022

Although UVB radiation is mainly absorbed by the epidermis, ~5–10% of its photons reach and affect the upper part of the dermis. Physiologically relevant UVB doses, able to provoke erythema, induce apoptosis in human dermal fibroblasts in vitro, as well as in the dermis of SKH-1 mice. Given the sparse and even contradictory existing information on the effect of UVB radiation on dermal fibroblasts’ viability, aim of this work was to unravel the crucial signaling pathways regulating the survival of UVB-treated human dermal fibroblasts. We found that UVB radiation immediately stimulates the phosphorylation of MAPK family members, as well as Akt, and is genotoxic leading to the delayed ATM-p53 axis activation. Akt phosphorylation after UVB radiation is EGFR-mediated and EGFR inhibition leads to a further decrease of viability, while the Akt activator SC79 rescues fibroblasts to an extent by a mechanism involving Nrf2 activation. The known Nrf2 activator sulforaphane also exerts a partial protective effect, although by acting in a distinct mechanism from SC79. On the other hand, inhibition of JNKs or of the ATM-p53 axis leads to a complete loss of viability after UVB irradiation. Interestingly, JNKs activation is necessary for p53 phosphorylation, while the ATM-p53 pathway is required for the long-term activation of JNKs and Akt, reassuring the protection from UVB. Although UVB radiation results in intense and prolonged increase of intracellular ROS levels, classical anti-oxidants, such as Trolox, are unable to affect Akt, JNKs, or p53 phosphorylation and to reverse the loss of fibroblasts’ viability. Collectively, here we provide evidence that the main viability-regulating UVB-triggered biochemical pathways act synergistically towards the protection of human dermal fibroblasts, with EGFR/Akt and Nrf2 serving as auxiliary anti-apoptotic machineries, while JNKs/ATM-p53 activation and interplay being overriding and indispensable for the perpetuation of cellular defense and the maintenance of cell viability.
Sunlight-driven nitrate loss records Antarctic surface mass balance
Authors: Akers Pete D. , Savarino Joël , Caillon Nicolas , Servettaz Aymeric P. M. , Le Meur Emmanuel , Magand Olivier , Martins Jean , Agosta Cécile , Crockford Peter , Kobayashi Kanon , Hattori Shohei , Curran Mark , van Ommen Tas , Jong Lenneke , Roberts Jason L.
Published: July 2022

Standard proxies for reconstructing surface mass balance (SMB) in Antarctic ice cores are often inaccurate or coarsely resolved when applied to more complicated environments away from dome summits. Here, we propose an alternative SMB proxy based on photolytic fractionation of nitrogen isotopes in nitrate observed at 114 sites throughout East Antarctica. Applying this proxy approach to nitrate in a shallow core drilled at a moderate SMB site (Aurora Basin North), we reconstruct 700 years of SMB changes that agree well with changes estimated from ice core density and upstream surface topography. For the under-sampled transition zones between dome summits and the coast, we show that this proxy can provide past and present SMB values that reflect the immediate local environment and are derived independently from existing techniques.
Extreme purifying selection against point mutations in the human genome
Authors: Dukler Noah , Mughal Mehreen R. , Ramani Ritika , Huang Yi-Fei , Siepel Adam
Published: July 2022

Large-scale genome sequencing has enabled the measurement of strong purifying selection in protein-coding genes. Here we describe a new method, called ExtRaINSIGHT, for measuring such selection in noncoding as well as coding regions of the human genome. ExtRaINSIGHT estimates the prevalence of “ultraselection” by the fractional depletion of rare single-nucleotide variants, after controlling for variation in mutation rates. Applying ExtRaINSIGHT to 71,702 whole genome sequences from gnomAD v3, we find abundant ultraselection in evolutionarily ancient miRNAs and neuronal protein-coding genes, as well as at splice sites. By contrast, we find much less ultraselection in other noncoding RNAs and transcription factor binding sites, and only modest levels in ultraconserved elements. We estimate that ~0.4–0.7% of the human genome is ultraselected, implying ~ 0.26–0.51 strongly deleterious mutations per generation. Overall, our study sheds new light on the genome-wide distribution of fitness effects by combining deep sequencing data and classical theory from population genetics.
Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement
Authors: Liu Jiaye , Wang Yang , Mu Chunyang , Li Meng , Li Kewei , Li Shan , Wu Wenshuang , Du Lingyao , Zhang Xiaoyun , Li Chuan , Peng Wei , Shen Junyi , Liu Yang , Yang Dujiang , Zhang Kaixiang , Ning Qingyang , Fu Xiaoying , Zeng Yu , Ni Yinyun , Zhou Zongguang , Liu Yi , Hu Yiguo , Zheng Xiaofeng , Wen Tianfu , Li Zhihui , Liu Yong
Published: July 2022

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.
Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC
Authors: Saddawi-Konefka Robert , O’Farrell Aoife , Faraji Farhoud , Clubb Lauren , Allevato Michael M. , Jensen Shawn M. , Yung Bryan S. , Wang Zhiyong , Wu Victoria H. , Anang Nana-Ama , Msari Riyam Al , Schokrpur Shiruyeh , Pietryga Ida Franiak , Molinolo Alfredo A. , Mesirov Jill P. , Simon Aaron B. , Fox Bernard A. , Bui Jack D. , Sharabi Andrew , Cohen Ezra E. W. , Califano Joseph A. , Gutkind J. Silvio
Published: July 2022

Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises the possibility that standard of care treatments delivered in concert may compromise the tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models in which we map tumor-draining lymphatics and develop models for regional lymphablation with surgery or radiation. We find that lymphablation eliminates the tumor ICI response, worsening overall survival and repolarizing the tumor- and peripheral-immune compartments. Mechanistically, within tumor-draining lymphatics, we observe an upregulation of conventional type I dendritic cells and type I interferon signaling and show that both are necessary for the ICI response and lost with lymphablation. Ultimately, we provide a mechanistic understanding of how standard oncologic therapies targeting regional lymphatics impact the tumor response to immune-oncology therapy in order to define rational, lymphatic-preserving treatment sequences that mobilize systemic antitumor immunity, achieve optimal tumor responses, control regional metastatic disease, and confer durable antitumor immunity.
Cell landscape of larval and adult Xenopus laevis at single-cell resolution
Authors: Liao Yuan , Ma Lifeng , Guo Qile , E Weigao , Fang Xing , Yang Lei , Ruan Fanwei , Wang Jingjing , Zhang Peijing , Sun Zhongyi , Chen Haide , Lin Zhongliang , Wang Xueyi , Wang Xinru , Sun Huiyu , Fang Xiunan , Zhou Yincong , Chen Ming , Shen Wanhua , Guo Guoji , Han Xiaoping
Published: July 2022

The rapid development of high-throughput single-cell RNA sequencing technology offers a good opportunity to dissect cell heterogeneity of animals. A large number of organism-wide single-cell atlases have been constructed for vertebrates such asHomo sapiens,Macaca fascicularis,Mus musculusandDanio rerio. However, an intermediate taxon that links mammals to vertebrates of more ancient origin is still lacking. Here, we construct the firstXenopuscell landscape to date, including larval and adult organs. Common cell lineage-specific transcription factors have been identified in vertebrates, including fish, amphibians and mammals. The comparison of larval and adult erythrocytes identifies stage-specific hemoglobin subtypes, as well as a common type of cluster containing both larval and adult hemoglobin, mainly at NF59. In addition, cell lineages originating from all three layers exhibits both antigen processing and presentation during metamorphosis, indicating a common regulatory mechanism during metamorphosis. Overall, our study provides a large-scale resource for research onXenopusmetamorphosis and adult organs.
Single-cell transcriptome atlas of the human corpus cavernosum
Authors: Zhao LiangYu , Han Sha , Su HengChuan , Li JianYing , Zhi ErLei , Li Peng , Yao ChenCheng , Tian RuHui , Chen HuiXing , Chen HuiRong , Luo JiaQiang , Shi ChenKun , Ji ZhiYong , Hu JianLin , Wu Gang , Zhou WeiDong , Tang YuXin , Chen YuZhuo , Lin GuiTing , Lue Tom F. , Wu DengLong , Li Zheng
Published: July 2022

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.
Integrin α3β1 promotes vessel formation of glioblastoma-associated endothelial cells through calcium-mediated macropinocytosis and lysosomal exocytosis
Authors: Bae Eunnyung , Huang Ping , Müller-Greven Gaёlle , Hambardzumyan Dolores , Sloan Andrew Edward , Nowacki Amy S. , Marko Nicholas , Carlin Cathleen R. , Gladson Candece L.
Published: July 2022

Therapeutic targeting of angiogenesis in glioblastoma has yielded mixed outcomes. Investigation of tumor-associated angiogenesis has focused on the factors that stimulate the sprouting, migration, and hyperproliferation of the endothelial cells. However, little is known regarding the processes underlying the formation of the tumor-associated vessels. To address this issue, we investigated vessel formation in CD31+ cells isolated from human glioblastoma tumors. The results indicate that overexpression of integrin α3β1 plays a central role in the promotion of tube formation in the tumor-associated endothelial cells in glioblastoma. Blocking α3β1 function reduced sprout and tube formation in the tumor-associated endothelial cells and vessel density in organotypic cultures of glioblastoma. The data further suggest a mechanistic model in which integrin α3β1-promoted calcium influx stimulates macropinocytosis and directed maturation of the macropinosomes in a manner that promotes lysosomal exocytosis during nascent lumen formation. Altogether, our data indicate that integrin α3β1 may be a therapeutic target on the glioblastoma vasculature.
Structure and assembly of cargo Rubisco in two native α-carboxysomes
Authors: Ni Tao , Sun Yaqi , Burn Will , Al-Hazeem Monsour M. J. , Zhu Yanan , Yu Xiulian , Liu Lu-Ning , Zhang Peijun
Published: July 2022

Carboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. They encapsulate Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase catalyzing carbon fixation inside a proteinaceous shell. How Rubisco complexes pack within the carboxysomes is unknown. Using cryo-electron tomography, we determine the distinct 3D organization of Rubisco inside two distant α-carboxysomes from a marine α-cyanobacterium Cyanobium sp. PCC 7001 where Rubiscos are organized in three concentric layers, and from a chemoautotrophic bacterium Halothiobacillus neapolitanus where they form intertwining spirals. We further resolve the structures of native Rubisco as well as its higher-order assembly at near-atomic resolutions by subtomogram averaging. The structures surprisingly reveal that the authentic intrinsically disordered linker protein CsoS2 interacts with Rubiscos in native carboxysomes but functions distinctively in the two α-carboxysomes. In contrast to the uniform Rubisco-CsoS2 association in the Cyanobium α-carboxysome, CsoS2 binds only to the Rubiscos close to the shell in the Halo α-carboxysome. Our findings provide critical knowledge of the assembly principles of α-carboxysomes, which may aid in the rational design and repurposing of carboxysome structures for new functions.
KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data
Authors: Crowl Sam , Jordan Ben T. , Ahmed Hamza , Ma Cynthia X. , Naegle Kristen M.
Published: July 2022

Kinase inhibitors as targeted therapies have played an important role in improving cancer outcomes. However, there are still considerable challenges, such as resistance, non-response, patient stratification, polypharmacology, and identifying combination therapy where understanding a tumor kinase activity profile could be transformative. Here, we develop a graph- and statistics-based algorithm, called KSTAR, to convert phosphoproteomic measurements of cells and tissues into a kinase activity score that is generalizable and useful for clinical pipelines, requiring no quantification of the phosphorylation sites. In this work, we demonstrate that KSTAR reliably captures expected kinase activity differences across different tissues and stimulation contexts, allows for the direct comparison of samples from independent experiments, and is robust across a wide range of dataset sizes. Finally, we apply KSTAR to clinical breast cancer phosphoproteomic data and find that there is potential for kinase activity inference from KSTAR to complement the current clinical diagnosis of HER2 status in breast cancer patients.
Dielectric catastrophe at the Wigner-Mott transition in a moiré superlattice
Authors: Tang Yanhao , Gu Jie , Liu Song , Watanabe Kenji , Taniguchi Takashi , Hone James C. , Mak Kin Fai , Shan Jie
Published: July 2022

The bandwidth-tuned Wigner-Mott transition is an interaction-driven phase transition from a generalized Wigner crystal to a Fermi liquid. Because the transition is generally accompanied by both magnetic and charge-order instabilities, it remains unclear if a continuous Wigner-Mott transition exists. Here, we demonstrate bandwidth-tuned metal-insulator transitions at fixed fractional fillings of a MoSe2/WS2 moiré superlattice. The bandwidth is controlled by an out-of-plane electric field. The dielectric response is probed optically with the 2s exciton in a remote WSe2 sensor layer. The exciton spectral weight is negligible for the metallic state with a large negative dielectric constant. It continuously vanishes when the transition is approached from the insulating side, corresponding to a diverging dielectric constant or a ‘dielectric catastrophe’ driven by the critical charge dynamics near the transition. Our results support the scenario of continuous Wigner-Mott transitions in two-dimensional triangular lattices and stimulate future explorations of exotic quantum phases in their vicinities.
Active multiband varifocal metalenses based on orbital angular momentum division multiplexing
Authors: Zheng Ruixuan , Pan Ruhao , Geng Guangzhou , Jiang Qiang , Du Shuo , Huang Lingling , Gu Changzhi , Li Junjie
Published: July 2022

Metalenses as miniature flat lenses exhibit a substantial potential in replacing traditional optical component. Although the metalenses have been intensively explored, their functions are limited by poor active ability, narrow operating band and small depth of field (DOF). Here, we show a dielectric metalens consisting of TiO2 nanofins array with ultrahigh aspect ratio to realize active multiband varifocal function. Regulating the orbital angular momentum (OAM) by the phase assignment covering the 2π range, its focal lengths can be switched from 5 mm to 35 mm. This active optical multiplexing uses the physical properties of OAM channels to selectively address and decode the vortex beams. The multiband capability and large DOFs with conversion efficiency of 49% for this metalens are validated for both 532 nm and 633 nm, and the incidence wavelength can further change the focal lengths. This non-mechanical tunable metalens demonstrates the possibility of active varifocal metalenses.
Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo
Authors: Benetti Natalia , Gouil Quentin , Tapia del Fierro Andres , Beck Tamara , Breslin Kelsey , Keniry Andrew , McGlinn Edwina , Blewitt Marnie E.
Published: July 2022

Parents transmit genetic and epigenetic information to their offspring. Maternal effect genes regulate the offspring epigenome to ensure normal development. Here we report that the epigenetic regulator SMCHD1 has a maternal effect onHoxgene expression and skeletal patterning. Maternal SMCHD1, present in the oocyte and preimplantation embryo, prevents precocious activation ofHoxgenes post-implantation. Without maternal SMCHD1, highly penetrant posterior homeotic transformations occur in the embryo.Hoxgenes are decorated with Polycomb marks H2AK119ub and H3K27me3 from the oocyte throughout early embryonic development; however, loss of maternal SMCHD1 does not deplete these marks. Therefore, we propose maternal SMCHD1 acts downstream of Polycomb marks to establish a chromatin state necessary for persistent epigenetic silencing and appropriateHoxgene expression later in the developing embryo. This is a striking role for maternal SMCHD1 in long-lived epigenetic effects impacting offspring phenotype.
Prediction of elevation of substantial fluctuation in coal seam floor based on surface spline function and its derivative
Authors: Yang Zhenwei , Xu Junyi , Xu Zhaofeng , Chen Jiangfeng
Published: July 2022

With the increasing depth of coal mining, the geological stress and structure becomes more and more complex. The elevation of No.8 coal floor significantly undulates in the studied coal mine. Even though a lot of boreholes have been drilled, it remains difficult to predict the spatial distribution features and it becomes challenging to plan the tunnel for the working face. Consequently, there has been a great loss of production in the coal mine, therefore, it is of great significance to study the prediction method for coal floor elevation of the working face. The surface spline function can be regarded as an infinite flat plate deformation in pure bending. The fluctuation of the coal floor can be considered to be the result of multi-period tectonic stress applied on the coal seam, so, the prediction of elevation of the coal floor with surface spline method is feasible. An advantage of surface spline method is that any order differentiable smooth surface can be obtained without regular known lattice and boundary derivatives. In the paper, the complete expression of surface spline function is derived, which is used to predict the elevation of No.8 coal floor of the coal mine. The results show that the trend of elevation of the coal floor can be extrapolated by known data, and the maximum error is 20 m, the minimum error is 0 m, and the error of 80% of the data is less than 3 m. The general trend of the coal floor has been predicted well. However, local peaks and valleys could not be predicted correctly, therefore, the first and second order derivative are projected to predict the peaks and valleys in the head of the tunneling.
Ascent of the conus medullaris in human foetuses: a systematic review and meta-analysis
Authors: Costa Almeida Lucas , de Souza Figueiredo Yasmin Juliany , Pinheiro Zylberman André , Garção Diogo Costa
Published: July 2022

The aim of the present systematic review and meta-analysis was to identify when the ascent of the conus medullaris occurs in human foetuses considering differences in evaluation methods and sample characteristics. Five databases were searched for relevant articles using different combinations of keywords. Article selection and data extraction were performed independently by two reviewers. Disagreements were resolved by a third reviewer. The variables were distributed into four groups according to the gestational age of the specimens: I (13–18 weeks); II (19–25 weeks); III (26–32 weeks); IV (33 weeks to the probable date of birth). Eighteen articles were included. The majority used imaging exams as the evaluation method. Cadaveric dissections were reported in the remaining articles. Only morphological studies were included in the meta-analysis. Significant ascent occurs between groups I and III as well as groups II and IV. Despite the considerable heterogeneity among the studies included in the present review, the findings enabled the determination that the conus medullaris reaches its normal birth level by the 26th week. Further analyses should be performed based on nationality and ethnicity to diminish the heterogeneity of the data.
Altered genome-wide hippocampal gene expression profiles following early life lead exposure and their potential for reversal by environmental enrichment
Authors: Singh G. , Singh V. , Kim T. , Ertel A. , Fu W. , Schneider J. S.
Published: July 2022

Early life lead (Pb) exposure is detrimental to neurobehavioral development. The quality of the environment can modify negative influences from Pb exposure, impacting the developmental trajectory following Pb exposure. Little is known about the molecular underpinnings in the brain of the interaction between Pb and the quality of the environment. We examined relationships between early life Pb exposure and living in an enriched versus a non-enriched postnatal environment on genome-wide transcription profiles in hippocampus CA1. RNA-seq identified differences in the transcriptome of enriched vs. non-enriched Pb-exposed animals. Most of the gene expression changes associated with Pb exposure were reversed by enrichment. This was also true for changes in upstream regulators, splicing events and long noncoding RNAs. Non-enriched rats also had memory impairments; enriched rats had no deficits. The results demonstrate that an enriched environment has a profound impact on behavior and the Pb-modified CA1 transcriptome. These findings show the potential for interactions between Pb exposure and the environment to result in significant transcriptional changes in the brain and, to the extent that this may occur in Pb-exposed children, could influence neuropsychological/educational outcomes, underscoring the importance for early intervention and environmental enrichment for Pb-exposed children.
Polarimetric biomarkers of peri-tumoral stroma can correlate with 5-year survival in patients with left-sided colorectal cancer
Authors: Lad Jigar , Serra Stefano , Quereshy Fayez , Khorasani Mohammadali , Vitkin Alex
Published: July 2022

Using a novel variant of polarized light microscopy for high-contrast imaging and quantification of unstained histology slides, the current study assesses the prognostic potential of peri-tumoral collagenous stroma architecture in 32 human stage III colorectal cancer (CRC) patient samples. We analyze three distinct polarimetrically-derived images and their associated texture features, explore different unsupervised clustering algorithm models to group the data, and compare the resultant groupings with patient survival. The results demonstrate an appreciable total accuracy of ~ 78% with significant separation (p < 0.05) across all approaches for the binary classification of 5-year patient survival outcomes. Surviving patients preferentially belonged to Cluster 1 irrespective of model approach, suggesting similar stromal microstructural characteristics in this sub-population. The results suggest that polarimetrically-derived stromal biomarkers may possess prognostic value that could improve clinical management/treatment stratification in CRC patients.
High-throughput screening of stable and efficient double inorganic halide perovskite materials by DFT
Authors: Diao Xinfeng , Diao Yongxin , Tang Yanlin , Zhao Gangling , Gu Qinzhong , Xie Yu , Shi Yebai , Zhu Ping , Zhang Liang
Published: July 2022

Perovskite solar cells have become the most promising third-generation solar cells because of their superior physical–chemical properties and high photoelectric conversion efficiency. However, the current obstacles to commercialization of perovskite solar cells are their poor stability and harmful elements. How to find high-efficiency, high-stability and non-toxic perovskite materials from thousands of possible perovskite crystals is the key to solve this problem. In this paper, the inorganic halide double perovskite A2BX6 and its crystal structure are considered, and the data mining algorithm in informatics is introduced into the high-throughput computing data to analyze various elements in nature to study the perovskite materials that can meet the requirements of high performance. The photoelectric conversion properties and stability of 42 inorganic double perovskite materials are studied based on density functional theory (DFT). The results show that the tolerance factors of 39 crystals are between 0.8 and 1.10, indicating that these crystals have stable perovskite structure. In addition, the dielectric function, PDOS, elastic modulus, shear modulus and poison’s ratio of these crystals are analyzed. According to the above theoretical simulation results, three candidate materials for ideal light absorption are presented. This can provide a theoretical basis for the industrial application of perovskite solar cells.
Substrate size-dependent conformational changes of bacterial pectin-binding protein crucial for chemotaxis and assimilation
Authors: Anamizu Kotaro , Takase Ryuichi , Hio Mamoru , Watanabe Daisuke , Mikami Bunzo , Hashimoto Wataru
Published: July 2022

Gram-negative Sphingomonas sp. strain A1 exhibits positive chemotaxis toward acidic polysaccharide pectin. SPH1118 has been identified as a pectin-binding protein involved in both pectin chemotaxis and assimilation. Here we show tertiary structures of SPH1118 with six different conformations as determined by X-ray crystallography. SPH1118 consisted of two domains with a large cleft between the domains and substrates bound to positively charged and aromatic residues in the cleft through hydrogen bond and stacking interactions. Substrate-free SPH1118 adopted three different conformations in the open form. On the other hand, the two domains were closed in substrate-bound form and the domain closure ratio was changed in response to the substrate size, suggesting that the conformational change upon binding to the substrate triggered the expression of pectin chemotaxis and assimilation. This study first clarified that the solute-binding protein with dual functions recognized the substrate through flexible conformational changes in response to the substrate size.
A pilot study to understand the relationship between cortical arousals and leg movements during sleep
Authors: Bansal Kanika , Garcia Javier , Feltch Cody , Earley Christopher , Robucci Ryan , Banerjee Nilanjan , Brooks Justin
Published: July 2022

Leg movements during sleep occur in patients with sleep pathology and healthy individuals. Some (but not all) leg movements during sleep are related to cortical arousals which occur without conscious awareness but have a significant effect of sleep fragmentation. Detecting leg movements during sleep that are associated with cortical arousals can provide unique insight into the nature and quality of sleep. In this study, a novel leg movement monitor that uses a unique capacitive displacement sensor and 6-axis inertial measurement unit, is used in conjunction with polysomnography to understand the relationship between leg movement and electroencephalogram (EEG) defined cortical arousals. In an approach that we call neuro-extremity analysis, directed connectivity metrics are used to interrogate causal linkages between EEG and leg movements measured by the leg movement sensors. The capacitive displacement measures were more closely related to EEG-defined cortical arousals than inertial measurements. Second, the neuro-extremity analysis reveals a temporally evolving connectivity pattern that is consistent with a model of cortical arousals in which brainstem dysfunction leads to near-instantaneous leg movements and a delayed, filtered signal to the cortex leading to the cortical arousal during sleep.
The prognostic value of neutrophil-to-lymphocyte ratio in cholangiocarcinoma: a systematic review and meta-analysis
Authors: Liu Dong , Heij Lara R. , Czigany Zoltan , Dahl Edgar , Dulk Marcel den , Lang Sven A. , Ulmer Tom F. , Neumann Ulf P. , Bednarsch Jan
Published: July 2022

The neutrophil-to-lymphocyte ratio (NLR) is used as biomarker in malignant diseases showing significant association with poor oncological outcomes. The main research question of the present study was whether NLR has also prognostic value in cholangiocarcinoma patients (CCA). A systematic review was carried out to identify studies related to NLR and clinical outcomes in CCA evaluating the literature from 01/2000 to 09/2021. A random-effects model, pooled hazard ratios (HR) and 95% confidence interval (CI) were used to investigate the statistical association between NLR and overall survival (OS) as well as disease-free survival (DFS). Subgroup analyses, evaluation of sensitivity and risk of bias were further carried out. 32 studies comprising 8572 patients were eligible for this systematic review and meta-analysis. The pooled outcomes revealed that high NLR prior to treatment is prognostic for poor OS (HR 1.28, 95% CI 1.18–1.38, p < 0.01) and DFS (HR 1.39, 95% CI 1.17–1.66, p < 0.01) with meaningful HR values. Subgroup analysis revealed that this association is not significantly affected by the treatment modality (surgical vs. non-surgical), NLR cut-off values, age and sample size of the included studies. Given the likelihood of NLR to be prognostic for reduced OS and DFS, pre-treatment NLR might serve as a useful biomarker for poor prognosis in patients with CCA and therefore facilitate clinical management.
Catulin reporter marks a heterogeneous population of invasive breast cancer cells with some demonstrating plasticity and participating in vascular mimicry
Authors: Gielata Mateusz , Karpińska Kamila , Gwiazdowska Aleksandra , Boryń Łukasz , Kobielak Agnieszka
Published: July 2022

Breast cancer is the most commonly diagnosed cancer in women worldwide. The activation of partial or more complete epithelial–mesenchymal transition in cancer cells enhances acquisition of invasive behaviors and expands their generation of cancer stem cells. Increased by EMT plasticity of tumor cells could promote vascular mimicry, a newly defined pattern of tumor microvascularization by which aggressive tumor cells can form vessel-like structures themselves. VM is strongly associated with a poor prognosis, but biological features of tumor cells that form VM remains unknown. Here we show that catulin is expressed in human BC samples and its expression correlates with the tumor progression. Ablation of catulin in hBC cell lines decreases their invasive potential in the 3D assays. Using a novel catulin promoter based reporter we tracked and characterized the small population of invasive BC cells in xenograft model. RNAseq analysis revealed enrichment in genes important for cellular movement, invasion and interestingly for tumor-vasculature interactions. Analysis of tumors unveiled that catulin reporter marks not only invasive cancer cells but also rare population of plastic, MCAM positive cancer cells that participate in vascular mimicry. Ablation of catulin in the xenograft model revealed deregulation of genes involved in cellular movement, and adhesive properties with striking decrease in CD44 which may impact stemness potential, and plasticity of breast cancer cells. These findings show directly that some plastic tumor cells can change the fate into endothelial-like, expressing MCAM and emphasize the importance of catulin in this process and breast cancer progression.
Altered resting-state functional connectivity within corticostriatal and subcortical-striatal circuits in chronic pain
Authors: Park Su Hyoun , Baker Anne K. , Krishna Vinit , Mackey Sean C. , Martucci Katherine T.
Published: July 2022

Brain corticostriatal circuits are important for understanding chronic pain and highly relevant to motivation and cognitive processes. It has been demonstrated that in patients with chronic back pain, altered nucleus accumbens (NAcc)—medial prefrontal cortex (MPFC) circuit fMRI-based activity is predictive of patient outcome. We evaluated the NAcc-MPFC circuit in patients with another chronic pain condition, fibromyalgia, to extend these important findings. First, we compared fMRI-based NAcc-MPFC resting-state functional connectivity in patients with fibromyalgia (N = 32) vs. healthy controls (N = 37). Compared to controls, the NAcc-MPFC circuit’s connectivity was significantly reduced in fibromyalgia. In addition, within the fibromyalgia group, NAcc-MPFC connectivity was significantly correlated with trait anxiety. Our expanded connectivity analysis of the NAcc to subcortical brain regions showed reduced connectivity of the right NAcc with mesolimbic circuit regions (putamen, thalamus, and ventral pallidum) in fibromyalgia. Lastly, in an exploratory analysis comparing our fibromyalgia and healthy control cohorts to a separate publicly available dataset from patients with chronic back pain, we identified reduced NAcc-MPFC connectivity across both the patient groups with unique alterations in NAcc-mesolimbic connectivity. Together, expanding upon prior observed alterations in brain corticostriatal circuits, our results provide novel evidence of altered corticostriatal and mesolimbic circuits in chronic pain.
Genome-wide variance quantitative trait locus analysis suggests small interaction effects in blood pressure traits
Authors: Shi Gang
Published: July 2022

Genome-wide variance quantitative trait loci (vQTL) analysis complements genome-wide association study (GWAS) and has the potential to identify novel variants associated with the trait, explain additional trait variance and lead to the identification of factors that modulate the genetic effects. I conducted genome-wide analysis of the UK Biobank data and identified 27 vQTLs associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). The top single-nucleotide polymorphisms (SNPs) are enriched for expression QTLs (eQTLs) or splicing QTLs (sQTLs) annotated by GTEx, suggesting their regulatory roles in mediating the associations with blood pressure (BP). Of the 27 vQTLs, 14 are known BP-associated QTLs discovered by GWASs. The heteroscedasticity effects of the 13 novel vQTLs are larger than their genetic main effects, which were not detected by existing GWASs. The total R-squared of the 27 top SNPs due to variance heteroscedasticity is 0.28%, compared with 0.50% owing to their main effects. The overall effect size of the variance heteroscedasticity is small in GWAS SNPs compared with their main effects. For the 411, 384 and 285 GWAS SNPs associated with SBP, DBP and PP, respectively, their heteroscedasticity effects were 0.52%, 0.43%, and 0.16%, and their main effects were 5.13%, 5.61%, and 3.75%, respectively. The number and effects of the vQTLs are small, which suggests that the effects of gene–environment and gene–gene interactions are small. The main effects of the SNPs remain the major source of genetic variance for BP, which would probably be true for other complex traits as well.