bluuebunny/crossref_metadata_2025 huggingface dataset:
Killing in the Name Of? Capital Punishment in Colonial and Postcolonial India
Authors: McClure Alastair
Published: October 2022

Unlike whipping, which was quickly abolished following independence, India has continued to hold tightly to the noose’s rope and remains a retentionist country to our present day. Notably, though the number of executions would fall dramatically in the first decades of India’s postcolonial history, the list of crimes made punishable by death has grown ever longer in recent years. Rather than positing the continued presence of the death penalty as an anachronism ill-suited for a modern democracy, this article takes seriously the legal and discursive developments that allowed the most infamous of penal institutions to travel safely across India’s twentieth century. From something that begun as a distilled expression of racialised colonial state power, like many other state institutions during this period, the death penalty would undergo a series of changes to remain relevant amidst new organizing political principles of representative democracy and popular will. Moving from the first formal efforts at abolition in the 1920s, through constitutional assembly debates in the 1940s, and Supreme Court judgements between 1967-83, the article positions capital punishment as a product of both deep colonial inheritances, and a particular process of postcolonial translation. Becoming fully couched in the language of popular sentiment by the culmination of this legal transformation, this violence would become well-positioned to grow within a national political culture increasingly organised around majoritarian expressions of national belonging.
Pubertal progression and its relationship to psychological and behavioral outcomes among adolescent boys
Authors: Tsai Meng-Che , Wang Yu-Chung Lawrence , Chan Hsun-Yu
Published: October 2022

Variations in pubertal timing and tempo have relevance to psychosocial development. Accounting for pubertal timing, tempo, and psychosocial development simultaneously in a model remains challenging. This study aimed to document the typology of pubertal development in a cohort of Taiwanese adolescent boys and then to examine how the associations between psychosocial variables across time vary by the patterns of pubertal development. A group of adolescent boys (n = 1,368) reported pubertal signs and psychosocial variables for 3 years since seventh grade. The growth mixture model revealed three major classes of pubertal transition: average pubertal growth, late-onset with rapid catch-up, and late-onset with slow catch-up. In a cross-lagged panel model, the multigroup analysis found the regression coefficients mostly invariant across all three classes, except those between deviant behavior and subsequent changes in depressive symptoms that were significantly positive only in the late-onset with slow catch-up group. Adolescent boys in this group were estimated to have the highest marginal level of depressive symptoms and deviant behavior in ninth grade among the three classes. Our study highlights the heterogeneity in boys’ pubertal development and the role of the pubertal development pattern in their psychosocial development.
Telling Our Own Story: A Bibliometrics Analysis of Mainland China’s Influence on Chinese Politics Research, 2001–2020
Authors: Fu Hui-Zhen , Shao Li
Published: October 2022

This study conducted a bibliometric analysis of Chinese politics research from 2001 to 2020 (N = 11,285) using Social Sciences Citation Index data. The number of publications in the field by scholars from Mainland China surged in the past 20 years; however, their influence on academia remained limited. Chinese institutions serve as the major hubs of collaborative networks. Using structural topic models, we identified 25 research topics that can be categorized in three clusters. In the past 20 years, scholars from Mainland China steered the focus of Chinese politics by causing a reduction in the proportion of international relation topics and an increase in the proportion of political economy topics. Domestic politics topics had the most citations. Scholars from Mainland China have made contributions to better research methods in the field. This article is a comprehensive view of Chinese politics research using a tool that is rarely used by political scientists. It depicts how studies of Chinese politics influence academia from a bibliometrics perspective.
Competition between form-related words in bilingual sentence reading: Effects of language proficiency
Authors: Pélissier Maud , Haugland Dag , Handeland Bjørn , Urland Beatrice Zitong , Wetterlin Allison , Wheeldon Linda , Frisson Steven
Published: October 2022

Sentence reading involves constant competition between lexical candidates. Previous research with monolinguals has shown that the neighbours of a read word are inhibited, making their retrieval as a subsequent target more difficult, but the duration of this interference may depend on reading skills. In this study, we examined neighbour priming effects in sentence reading among proficient Norwegian–English bilinguals reading in their L2. We investigated the effects of the distance between prime and target (short vs. long) and the nature of the overlap between the two words (beginning or end), and related these to differences in individual cognitive skills. Our results replicated the inhibition effects found in monolinguals, albeit slightly delayed. Interference between form-related words was affected by the L2 reading skills and, crucially, by the phonological decoding abilities of the bilingual reader. We discuss the results in light of competition models of bilingual reading as well as episodic memory accounts.
Evaluation of the Plasticity of Novel Regulatory Cells—Telocytes—in the Gonad of the Male Chinese Soft-Shelled Turtle (Pelodiscus sinensis) Associated with Seasonal Reproductive Activity
Authors: Meng Xiangfei , Ding Baitao , Zhu Zhaoxuan , Ma Qianhui , Wang Qi , Feng Yongchao , Liu Yue , Wang Jia , Yang Ping
Published: October 2022

Telocyte (TC)—a new type of interstitial cell with long telopodes, can form cellular junctions with various tissues or cells to participate in the regulation of multitudes of physiological activities and diseases. This study aimed to characterize the morphology, molecular features, and potential functions of hormone regulation in Chinese soft-shelled turtle (Pelodiscus sinensis) testis TCs at different reproductive stages by histological evaluation, immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy. During hibernation, TCs were widely distributed in the interstitial tissue. In contrast, during reproductive activity, TCs were noted to be in close proximity with peritubular myoid cells surrounding the seminiferous tubule. Moreover, formed cell–cell junctions were observed between TCs and PTMs. The results of IHC and IF showed that the immunophenotype of testicular TCs in hibernating Chinese soft-shelled turtles is CD34+Vimentin−, while the reproductive telopodes (Tps) show low expression of vimentin. The androgen receptor is expressed in Tps of TCs of testis during hibernation. Our results showed also that TCs in seasonal breeding animals regulate the activity of neighboring cells by releasing extracellular microvesicles (EXMVs), thus influencing the activity of spermatogenesis and steroidogenesis. Consideration of our novel and interesting results indicate that the whole area warrants further research.
From invisibility to positive legal protection: The drafting of Article 11 of the Convention on the Rights of Persons with Disabilities
Authors: Begg Andrew
Published: October 2022

Initial drafts of the Convention on the Rights of Persons with Disabilities (CRPD) did not include any significant reference to the obligations of States to protect their citizens with disabilities during armed conflict or other emergency situations; international documents dealing with disability up until that point had not considered persons with disabilities as rights holders during armed conflict either. But early in the negotiations for the CRPD, disabled persons’ organizations made it clear that they wanted to see the protections of the Convention extend to times of risk, emergency and armed conflict.

This study focuses on Article 11 of the CRPD. The negotiating history of Article 11 demonstrates that although there were some disagreements over the scope of the article, support for a clear statement of States’ obligations during armed conflict and other emergencies was broad-based and came from all regions.
Relational legal pluralism and Indigenous legal orders in Canada
Authors: McKerracher Kelty
Published: October 2022

The survival and resurgence of Indigenous legal orders and constitutional traditions in Canada, as elsewhere, disrupt the normative hegemony of the liberal state and articulate a constitutionalism that accounts for a plurality of laws. How can state and non-state legal orders interact across vastly different normative worlds? How can their interaction address the colonial power imbalance and what role should recognition play in this relationship? This article draws on the work of Ralf Michaels on relational legal pluralism and Aaron Mills on Anishinaabe constitutionalism to explore how a legally plural society must embrace Michaels’ challenge of constitutive external recognition: the idea that legal orders mutually constitute each other through recognition without interfering with each other’s factual status as law. External recognition is consistent with strong legal pluralism and is distinct from recognition within the multicultural liberal state, a form of weak legal pluralism and continued colonialism. Mills’ discussion of treaty, rather than contract, as a foundation for shared political community assists in imagining a constitutionalism with/in Canada in which distinct legal orders can mutually constitute each other without domination. Linkage norms may help to establish reciprocal relations among state law and Indigenous legal orders, and the enactment of such ‘tertiary rules of recognition’ from within Indigenous legal orders may itself shift the balance of power.
Soziale Netzwerke von Kindern mit psychischen Störungen
Authors: Titze Karl , Jaite Charlotte , Winter Sibylle Maria
Published: October 2022

Zusammenfassung. Die Studie vergleicht die sozialen Netzwerke von Kindern mit psychischen Störungen mit einer nichtklinischen parallelisierten Vergleichsgruppe ( n = 75/75, männlich 69 %/69 %, Alter: 9.4/9.0 Jahre). Zudem wurden die Quantität und Struktur der sozialen Netzwerke sowie Belastungen und Ressourcen in der Patientengruppe allgemein und bei spezifischen Störungen (hyperkinetische Störung [HKS] und emotionale Störung des Kindesalters) untersucht. Die sozialen Netze wurden mit einer Revision des Sozialen Beziehungstests für Kinder (SoBeKi-R) und die psychischen Störungen über klinische Diagnosen, Child Behavior Checklist und Strengths and Difficulties Questionnaire erfasst. Die Patient_innen berichteten von insgesamt kleineren Netzwerken ( AM/SD: 13.7/4.9 vs. 15.8/5.2) und signifikant geringeren sozialen Ressourcen als die Vergleichsgruppe, v. a. im außerfamiliären Bereich. Während bei emotionalen Störungen sogar von weniger sozialen Belastungen als in der Vergleichsgruppe berichtet wurde, hatten Kinder mit HKS pro Netzwerkperson tendenziell höhere Belastungswerte; externalisierende Symptome waren hingegen deutlicher mit höheren Belastungen im sozialen Netz assoziiert. Die je nach Störungsbild unterschiedlichen Ergebnisse deuten darauf hin, dass komplexe störungsspezifische Zusammenhänge zwischen den Syndromen und den berichteten Ressourcen und Belastungen im sozialen Netz bestehen.
Recent Changes of Phytoplankton Bloom Phenology in the Northern High‐Latitude Oceans (2003–2020)
Authors: Zhao Haipeng , Matsuoka Atsushi , Manizza Manfredi , Winter Amos
Published: October 2022

Eighteen years (2003–2020) of data on remotely‐sensed ocean color in high northern latitudes show a significant increase (0.56% yr−1) in double blooms of phytoplankton. Starting in 2015 the rate of increase rose to 1.10% yr−1. Double blooms have become especially prevalent in regions north of 50°N in the North Atlantic, Gulf of Alaska and southern Chukchi Sea. Our correlation analysis suggests that double bloom occurrences are dependent on latitude and seasonal changes in both sea surface temperature (SST) and mixed layer depth (MLD), particularly in the subpolar North Pacific (SNP) and polar oceans (65°–75°N), although we cannot attribute the increased double blooms to specific causes. Single blooms indicated by Chlorophyll a (Chl a) dominate in subpolar‐polar waters and occur close to the timing of the Particulate Inorganic Carbon (PIC) peak (i.e., June–August). In the SNP single bloom, Chl a peaks occur earlier than PIC peaks. This interval was shorter during 2016–2020, which is associated with warming anomalies. In the southern part of the Chukchi Sea, however, we found that PIC peaks occur earlier than Chl a peaks, suggesting a potentially different succession pattern between calcifiers and other functional groups. We speculate that in the near future double blooms of phytoplankton will become a prevalent feature in high‐latitude oceans with concurrent changes in the timing of blooms and seasonal phytoplankton succession in the surface ocean due to climate change.
Slight Shifts in Magnetic Field Preceded California Earthquakes
Authors: Learn Joshua
Published: October 2022

Magnetometers detected faint signals that with further study, may improve our understanding of what happens before earthquakes and offer promise for early detection.
The 2021 Mw 7.3 East Cape Earthquake: Triggered Rupture in Complex Faulting Revealed by Multi‐Array Back‐Projections
Authors: Xie Y. , Meng L. , Zhou T. , Xu L. , Bao H. , Chu R.
Published: October 2022

On 04 March 2021 the Mw 7.3 East Cape, New Zealand earthquake occurred at the southern end of the Kermadec Trench. The United States Geological Survey W‐phase solution shows an unexpected focal mechanism compared to historical earthquakes. We combine earthquake back‐projections of 4 arrays to image the kinematic process of the Mw 7.3 earthquake. Our results reveal a bilateral rupture predominantly propagating upward at a slow speed of 1 km/s and a triggered rupture at ∼10 km, corresponding to the deep reverse faulting event at 70 km and a triggered shallow normal faulting event (∼20 km) resolved by previous subevent and finite fault inversions. The epicenter and a group of aftershocks are deeper than the bottom of the slab according to a regional tomography model. Such deep failure is possibly enabled by a delaminating lower crust of the Hikurangi plateau.
Using CMIP6 Models to Assess the Significance of the Observed Trend in the Atlantic Meridional Overturning Circulation
Authors: Kelson R. L. , Straub D. N. , Dufour C. O.
Published: October 2022

Observations from the RAPID array at 26.5°N suggest a weakening in the Atlantic meridional overturning circulation between 2004 and 2020. The shortness of this time series raises the question of whether this weakening should be thought of as natural variability or as related to climate change. To estimate natural variability, preindustrial control runs of the Coupled Model Intercomparison Project Phase 6 are used and the observed weakening is found to fall within the distribution of naturally occurring trends. These trends result from model variability on periods longer than the observational window, and variation between models at these frequencies is especially pronounced. Finally, adding noise to inflate model variability also inflates model trends; however, the effect on trends is sensitive only to the low frequency portion of the noise spectrum.
Detrainment Dominates CCN Concentrations Around Non‐Precipitating Convective Clouds Over the Amazon
Authors: Braga Ramon C. , Rosenfeld Daniel , Andreae Meinrat O. , Pöhlker Christopher , Pöschl Ulrich , Voigt Christiane , Weinzierl Bernadett , Wendisch Manfred , Pöhlker Mira L. , Harrison Daniel
Published: October 2022

We investigated the relationship between the number concentration of cloud droplets (Nd) in ice‐free convective clouds and of particles large enough to act as cloud condensation nuclei (CCN) measured at the lateral boundaries of cloud elements. The data were collected during the ACRIDICON‐CHUVA aircraft campaign over the Amazon Basin. The results indicate that the CCN particles at the lateral cloud boundaries are dominated by detrainment from the cloud. The CCN concentrations detrained from non‐precipitating convective clouds are smaller compared to below cloud bases. The detrained CCN particles from precipitating cloud volumes have relatively larger sizes, but lower concentrations. Our findings indicate that CCN particles ingested from below cloud bases are activated into cloud droplets, which evaporate at the lateral boundaries and above cloud base and release the CCN again to ambient cloud‐free air, after some cloud processing. These results support the hypothesis that the CCN around the cloud are cloud‐processed.
Microphysical Differences in the Concentric Eyewalls of Typhoon Lekima (2019)
Authors: Bao Xuwei , Zhang Shuai , Liang Yan
Published: October 2022

Using polarimetric radar observations, different microphysical characteristics were found in the asymmetric concentric eyewalls of Typhoon Lekima (2019). In addition to the differential reflectivity (ZDR) column, a typical size‐sorting radar signature was evident in the upright inner eyewall: a cyclonically upwind offset of the ZDR maximum relative to the horizontal reflectivity (ZH) and specific differential phase (KDP) maxima. In contrast, the large values of ZDR were located above the melting layer along the upper edge of the more tilted outer eyewall and did not extend downward to form a ZDR column. In the cyclonic direction, moreover, the large values of the three polarimetric variables in the outer eyewall almost overlapped, without the cyclonic offset of typical size‐sorting radar signature. Thus, more active warm‐cloud (cold‐cloud) processes dominate in the outer (inner) eyewall, particularly for the production of large drops, closely associated with the intrinsic dynamical structure of the concentric eyewalls.
Geophysical Evidence for Magmatism Southwest of the Brothers Islands, Northern Red Sea (Offshore Quseir, Egypt)
Authors: Ali Moamen , Ligi Marco , Ceriani Andrea , Bouchaala Fateh , Bosworth William , Decarlis Alessandro
Published: October 2022

The Red Sea formed as a consequence of Cenozoic rifting between the African and Arabian plates. While continuous oceanic spreading is active in the southern and central sectors, in the northern Red Sea, exposure of oceanic crust is limited to a few along‐axis isolated deeps. However, several off‐axis magmatic edifices have been recognized in this sector, their description in terms of relative age and architectural features remains vague. One of these, offshore Quseir corresponding to a kilometer‐size structural high, was studied in detail using 3D industrial seismic data. This structure is interpreted as due to the coalescence of different volcanic edifices developed on the footwall of a major rift‐related normal fault. Magnetic and gravity data and forward modeling suggest a volcanic nature of the substratum underlying the morphological relief. A similar volcanic origin is proposed for other neighboring basement hills that show a similar magnetic signal. Relationships with the imaged seismo‐stratigraphic sequences point to a Pleistocene age for the magmatic event. Arabian alkali‐basalts, at the same latitude as Quseir, show ages comparable to those inferred for the volcano edifice studied, suggesting a similar geotectonic context. In western Arabian plate, large alkali‐lava fields (Harrats) developed along rift‐related faults since the early stages of the Red Sea rift (Late Oligocene). They display a significant northward rejuvenation trend that may be explained by the progressive propagation of the Afar mantle plume.
SWAT_DA: Sequential Multivariate Data Assimilation‐Oriented Modification of SWAT
Authors: Bayat Mehrad , Alizadeh Hosein , Mojaradi Barat
Published: October 2022

Multivariate data assimilation (DA), a novel way to couple big data with land surface models, was extensively employed in forecasting‐reanalyzing systems (FRSs), for example, ECMWF and GLDAS. Meanwhile, most (distributed) hydrological models, like soil and water assessment tool (SWAT), have not been equipped with straightforward ways to link to DA algorithms. Therefore, it is one of the main barriers to utilizing such hydrological models in FRSs. This paper deals with multivariate DA into SWAT (DA‐SWAT), which is complicated since the original model does not provide full access to the models' initial conditions (ICs) at the hydrologic response unit (HRU) scale. The preceding DA‐SWAT works commonly used an integrated approach in which the DA and SWAT codes were implemented in the same programming environment. We discuss how this approach complicates and prevents the application of DA‐SWAT in multivariate, multimodel, and multisensor systems. Accordingly, we proposed a new approach for DA‐SWAT by which SWAT can be perfectly linked with any DA algorithm of interest coded in any desired programming environment. Our framework utilizes input/output text files to access ICs and to link DA with SWAT. Moreover, we designed some univariate and multivariate scenarios for assimilating in situ streamflow measurement and MODIS's snow cover fraction (SCF) data, which has not yet been focused on in the SWAT calibration context. Results show that compared to the univariate assimilation of streamflow (SCF), the multivariate assimilation mitigates the equifinality problem and more accurately estimates SCF (streamflow) by improving NS and PBIAS measures with the differences of 0.4 (0.86), 12% (64%), respectively.
A MYC-ZNF148-ID1/3 regulatory axis modulating cancer stem cell traits in aggressive breast cancer
Authors: Kim Mijeong , Singh Manjot , Lee Bum-Kyu , Hibbs Moira , Richardson Kirsty , Ellies Lesley , Wintle Larissa , Stuart Lisa M. , Wang Jenny Y. , Voon Dominic C. , Blancafort Pilar , Wang Jianlong , Kim Jonghwan , Leedman Peter J. , Woo Andrew J.
Published: October 2022

The MYC proto-oncogene (MYC) is one of the most frequently overexpressed genes in breast cancer that drives cancer stem cell-like traits, resulting in aggressive disease progression and poor prognosis. In this study, we identified zinc finger transcription factor 148 (ZNF148, also called Zfp148 and ZBP-89) as a direct target of MYC. ZNF148 suppressed cell proliferation and migration and was transcriptionally repressed by MYC in breast cancer. Depletion of ZNF148 by short hairpin RNA (shRNA) and CRISPR/Cas9 increased triple-negative breast cancer (TNBC) cell proliferation and migration. Global transcriptome and chromatin occupancy analyses of ZNF148 revealed a central role in inhibiting cancer cell de-differentiation and migration. Mechanistically, we identified the Inhibitor of DNA binding 1 and 3 (ID1, ID3), drivers of cancer stemness and plasticity, as previously uncharacterized targets of transcriptional repression by ZNF148. Silencing of ZNF148 increased the stemness and tumorigenicity in TNBC cells. These findings uncover a previously unknown tumor suppressor role for ZNF148, and a transcriptional regulatory circuitry encompassing MYC, ZNF148, and ID1/3 in driving cancer stem cell traits in aggressive breast cancer.
Utilizing ferrorestorable polarization in energy-storage ceramic capacitors
Authors: Matsuo Hiroki , Utsunomiya Masashi , Noguchi Yuji
Published: October 2022

A self-powered system with a long lifetime would represent an opportunity in the development of a next-generation, standalone Internet of Things. Ceramic capacitors are promising candidates for energy storage components because of their stability and fast charge/discharge capabilities. However, even the energy density of state-of-the-art capacitors needs to be increased markedly for this application. Improving the breakdown electric field represents a potential solution, but operations at such high fields relying on unchanged dielectric permittivity sacrifice the lifetime of the capacitor to some degree. Here, we report ferrorestorable polarization engineering capable of more than doubling the effective permittivity. Our experiments and ab initio calculations demonstrate that a defect dipole composed of Cu3+ and oxygen vacancy in a prototypical ferroelectric BaTiO3 ceramic is coupled with spontaneous polarization. The resultant ferrorestorable polarization delivers an extraordinarily large effective relative permittivity, beyond 7000, with a high energy efficiency up to 89%. Our work paves the way to realizing efficient ceramic capacitors for self-powered applications.
Assembling defined DNA nanostructures with anticancer drugs: a metformin/DNA complex nanoplatform with a synergistic antitumor effect for KRAS-mutated lung cancer therapy
Authors: Qian Hang , Wang Dong , He Binfeng , Liu Qian , Xu Yu , Wu Di , Chen Chunfa , Zhang Wen , Leong David Tai , Wang Guansong
Published: October 2022

Herein, a strategy is proposed to simultaneously deliver the small-molecule drug metformin and siRNA with self-assembled DNA nanostructures. The biomedical application of DNA nanostructures is highly promising but still in its infancy. DNA nanostructures as drug delivery vehicles are conventionally synthesized in a magnesium-containing buffer. We propose using an anticancer drug to assemble DNA nanostructures and deliver them with siRNA for synergistic anticancer therapy. The metformin cargo induces DNA self-assembly into well-defined, uniform nanostructures, producing a drug–DNA nanocomplex with multiple functionalities for cancer therapy. Both tile-based and DNA origami structures can be assembled with metformin. The as-prepared metformin/DNA nanocomplex showed high structural and thermal stability and enzymatic resistance in physiological settings. The metformin in the nanocomplex and the KRASG12C siRNA exerted a strong, synergistic antitumor effect against KRAS-mutated non-small cell lung cancer (NSCLC) both in vitro and in vivo by suppressing the RAS/AKT/mTOR and AMPK/AKT/mTOR signaling pathways. The current study suggests that the assembly of complex DNA nanomaterials with carefully chosen small molecules is key to endowing DNA nanostructures with new functionalities and subsequently expanding their applications in multidisciplinary research fields.
Characteristics and treatment response of polypoidal choroidal vasculopathy in highly myopic eyes
Authors: Huang Wei-Lun , Hsia Yun , Wang Shih-Wen , Hung Kuo-Chi , Huang Chien-Jung , Chen Muh-Shy , Ho Tzyy-Chang
Published: October 2022

Background

To compare the characteristics and treatment responses of polypoidal choroidal vasculopathy (PCV) between highly myopic and non-highly myopic eyes.

Methods

This retrospective cohort study included patients diagnosed with PCV at the clinic of National Taiwan University Hospital between 2013 and 2019. The diseased eyes were grouped per refractive error and axial length at diagnosis. Imaging data were used to retrieve the PCV characteristics, and electronic medical records were used to retrieve the treatment responses.

Results

Among 116 eyes with PCV, 11 eyes of 10 patients were highly myopic; seven of these patients were women. All highly myopic eyes showed a thin subfoveal choroid, while three eyes had a pachychoroid phenotype with significant focal choroidal thickening. After treatment with either intravitreal anti-vascular endothelial growth factor (VEGF) injections, photodynamic therapy (PDT), or both, best-corrected visual acuity was better in the high-myopia group at 1 year. Visual acuity at presentation and the presence of feeder vessels were found to be predictors of the visual outcome.

Conclusions

In this study we reported, to the best of our knowledge, the largest cohort of PCV in highly myopic eyes to date. Female predominance, lower incidence of subretinal haemorrhage, and a thin choroid with a focal pachychoroid phenotype were found to characterise PCV in highly myopic eyes. Visual acuity transiently improved after either anti-VEGF monotherapy or combination therapy with PDT.
Practical implementation of a q4–q16 aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration: Updated guidance from a UK expert panel
Authors: Bailey Clare , Cackett Peter , Kotagiri Ajay , Mahmood Sajjad , Minos Evangelos , Narendran Nirodhini , Patwardhan Ashish , Sim Dawn A. , Morgan-Warren Peter , O’Neil Carolyn , Straw Katie
Published: October 2022

Objectives

This report, based on guidance from a panel of UK retina specialists, introduces a revised intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) pathway for the treatment of neovascular age-related macular degeneration (nAMD). The T&E pathway incorporates the updated IVT-AFL label (April 2021) allowing flexible treatment intervals of 4 weeks to 16 weeks, after three initiation doses and a further dose after 8 weeks. Practical guidance is provided on the clinical implementation of the revised pathway, with the aim of supporting clinical decision-making to benefit patients and addressing capacity issues in nAMD services.

Methods

Three structured round-table meetings of UK retina specialists were held online on 19 May, 16 June and 13 October 2021. These meetings were organised and funded by Bayer.

Results

The authors revised the previously published consensus pathway to reflect the changes to the IVT-AFL label and developed guidelines for the implementation of the pathway in UK clinical practice. The guidelines include topics such as recommendations for extending patients with 2- or 4-week adjustments, extending patients to 16-week treatment intervals, managing fellow eye involvement, and reducing treatment intervals for patients with particularly active disease.

Conclusions

The revised IVT-AFL T&E nAMD pathway offers guidance to clinicians seeking to increase the dosing flexibility of IVT-AFL, with 4- to 16-week treatment intervals, in line with the updated IVT-AFL label, to meet the continually evolving demands of nAMD service provision.
GWAS, MWAS and mGWAS provide insights into precision agriculture based on genotype-dependent microbial effects in foxtail millet
Authors: Wang Yayu , Wang Xiaolin , Sun Shuai , Jin Canzhi , Su Jianmu , Wei Jinpu , Luo Xinyue , Wen Jiawen , Wei Tong , Sahu Sunil Kumar , Zou Hongfeng , Chen Hongyun , Mu Zhixin , Zhang Gengyun , Liu Xin , Xu Xun , Gram Lone , Yang Huanming , Wang Ertao , Liu Huan
Published: October 2022

Genetic and environmental factors collectively determine plant growth and yield. In the past 20 years, genome-wide association studies (GWAS) have been conducted on crops to decipher genetic loci that contribute to growth and yield, however, plant genotype appears to be insufficient to explain the trait variations. Here, we unravel the associations between genotypic, phenotypic, and rhizoplane microbiota variables of 827 foxtail millet cultivars by an integrated GWAS, microbiome-wide association studies (MWAS) and microbiome genome-wide association studies (mGWAS) method. We identify 257 rhizoplane microbial biomarkers associated with six key agronomic traits and validated the microbial-mediated growth effects on foxtail millet using marker strains isolated from the field. The rhizoplane microbiota composition is mainly driven by variations in plant genes related to immunity, metabolites, hormone signaling and nutrient uptake. Among these, the host immune gene FLS2 and transcription factor bHLH35 are widely associated with the microbial taxa of the rhizoplane. We further uncover a plant genotype-microbiota interaction network that contributes to phenotype plasticity. The microbial-mediated growth effects on foxtail millet are dependent on the host genotype, suggesting that precision microbiome management could be used to engineer high-yielding cultivars in agriculture systems.
High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci
Authors: Marchal Claire , Singh Nivedita , Batz Zachary , Advani Jayshree , Jaeger Catherine , Corso-Díaz Ximena , Swaroop Anand
Published: October 2022

Chromatin organization and enhancer-promoter contacts establish unique spatiotemporal gene expression patterns in distinct cell types. Non-coding genetic variants can influence cellular phenotypes by modifying higher-order transcriptional hubs and consequently gene expression. To elucidate genomic regulation in human retina, we mapped chromatin contacts at high resolution and integrated with super-enhancers (SEs), histone marks, binding of CTCF and select transcription factors. We show that topologically associated domains (TADs) with central SEs exhibit stronger insulation and augmented contact with retinal genes relative to TADs with edge SEs. Merging genome-wide expression quantitative trait loci (eQTLs) with topology map reveals physical links between 100 eQTLs and corresponding eGenes associated with retinal neurodegeneration. Additionally, we uncover candidate genes for susceptibility variants linked to age-related macular degeneration and glaucoma. Our study of high-resolution genomic architecture of human retina provides insights into genetic control of tissue-specific functions, suggests paradigms for missing heritability, and enables the dissection of common blinding disease phenotypes.
Observation of boundary induced chiral anomaly bulk states and their transport properties
Authors: Wang Mudi , Ma Qiyun , Liu Shan , Zhang Ruo-Yang , Zhang Lei , Ke Manzhu , Liu Zhengyou , Chan C. T.
Published: October 2022

The most useful property of topological materials is perhaps the robust transport of topological edge modes, whose existence depends on bulk topological invariants. This means that we need to make volumetric changes to many atoms in the bulk to control the transport properties of the edges in a sample. We suggest here that we can do the reverse in some cases: the properties of the edge can be used to induce chiral transport phenomena in some bulk modes. Specifically, we show that a topologically trivial 2D hexagonal phononic crystal slab (waveguide) bounded by hard-wall boundaries guarantees the existence of bulk modes with chiral anomaly inside a pseudogap due to finite size effect. We experimentally observed robust valley-selected transport, complete valley state conversion, and valley focusing of the chiral anomaly bulk states (CABSs) in such phononic crystal waveguides. The same concept also applies to electromagnetics.
Covalent bond shortening and distortion induced by pressurization of thorium, uranium, and neptunium tetrakis aryloxides
Authors: Shephard Jacob J. , Berryman Victoria E. J. , Ochiai Tatsumi , Walter Olaf , Price Amy N. , Warren Mark R. , Arnold Polly L. , Kaltsoyannis Nikolas , Parsons Simon
Published: October 2022

Covalency involving the 5f orbitals is regularly invoked to explain the reactivity, structure and spectroscopic properties of the actinides, but the ionic versus covalent nature of metal-ligand bonding in actinide complexes remains controversial. The tetrakis 2,6-di-tert-butylphenoxide complexes of Th, U and Np form an isostructural series of crystal structures containing approximately tetrahedral MO4 cores. We show that up to 3 GPa the Th and U crystal structures show negative linear compressibility as the OMO angles distort. At 3 GPa the angles snap back to their original values, reverting to a tetrahedral geometry with an abrupt shortening of the M-O distances by up to 0.1 Å. The Np complex shows similar but smaller effects, transforming above 2.4 GPa. Electronic structure calculations associate the M-O bond shortening with a change in covalency resulting from increased contributions to the M-O bonding by the metal 6d and 5f orbitals, the combination promoting MO4 flexibility at little cost in energy.
Migration of solidification grain boundaries and prediction
Authors: Liu Hongmei , Lu Shenglu , Zhang Yingbo , Chen Hui , Chen Yungui , Qian Ma
Published: October 2022

Solidification processing is essential to the manufacture of various metal products, including additive manufacturing. Solidification grain boundaries (SGBs) result from the solidification of the last liquid film between two abutting grains of different orientations. They can migrate, but unlike normal GB migration, SGB migration (SGBM) decouples SGBs from solidification microsegregation, further affecting material properties. Here, we first show the salient features of SGBM in magnesium-tin alloys solidified with cooling rates of 8−1690 °C/s. A theoretical model is then developed for SGBM in dilute binary alloys, focusing on the effect of solute type and content, and applied to 10 alloy systems with remarkable agreement. SGMB does not depend on cooling rate or time but relates to grain size. It tends to occur athermally. The findings of this study extend perspectives on solidification grain structure formation and control for improved performance (e.g. hot or liquation cracking during reheating, intergranular corrosion or fracture).
Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis
Authors: Huang Hanyao , Pan Weiyi , Wang Yifan , Kim Hye Sung , Shao Dan , Huang Baoding , Ho Tzu-Chieh , Lao Yeh-Hsing , Quek Chai Hoon , Shi Jiayu , Chen Qianming , Shi Bing , Zhang Shengmin , Zhao Lei , Leong Kam W.
Published: October 2022

Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samples, we test the hypothesis that the cfDNA-scavenging approach will benefit periodontitis treatment. We create a nanoparticulate cfDNA scavenger specific for periodontitis by coating selenium-doped hydroxyapatite nanoparticles (SeHANs) with cationic polyamidoamine dendrimers (PAMAM-G3), namely G3@SeHANs, and compare the activities of G3@SeHANs with those of soluble PAMAM-G3 polymer. Both G3@SeHANs and PAMAM-G3 inhibit periodontitis-related proinflammation in vitro by scavenging cfDNA and alleviate inflammatory bone loss in a mouse model of ligature-induced periodontitis. G3@SeHANs also regulate the mononuclear phagocyte system in a periodontitis environment, promoting the M2 over the M1 macrophage phenotype. G3@SeHANs show greater therapeutic effects than PAMAM-G3 in reducing proinflammation and alveolar bone loss in vivo. Our findings demonstrate the importance of cfDNA in periodontitis and the potential for using hydroxyapatite-based nanoparticulate cfDNA scavengers to ameliorate periodontitis.
Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis
Authors: Boland Sebastian , Swarup Sharan , Ambaw Yohannes A. , Malia Pedro C. , Richards Ruth C. , Fischer Alexander W. , Singh Shubham , Aggarwal Geetika , Spina Salvatore , Nana Alissa L. , Grinberg Lea T. , Seeley William W. , Surma Michal A. , Klose Christian , Paulo Joao A. , Nguyen Andrew D. , Harper J. Wade , Walther Tobias C. , Farese Robert V.
Published: October 2022

Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN-mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. In these cells and tissues, levels of lysosomal enzymes that catabolize gangliosides were normal, but levels of bis(monoacylglycero)phosphates (BMP), lipids required for ganglioside catabolism, were reduced with PGRN deficiency. Our findings indicate that granulins are required to maintain BMP levels to support ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.
Search and processing of Holliday junctions within long DNA by junction-resolving enzymes
Authors: Kaczmarczyk Artur P. , Déclais Anne-Cécile , Newton Matthew D. , Boulton Simon J. , Lilley David M. J. , Rueda David S.
Published: October 2022

Resolution of Holliday junctions is a critical intermediate step of homologous recombination in which junctions are processed by junction-resolving endonucleases. Although binding and cleavage are well understood, the question remains how the enzymes locate their substrate within long duplex DNA. Here we track fluorescent dimers of endonuclease I on DNA, presenting the complete single-molecule reaction trajectory for a junction-resolving enzyme finding and cleaving a Holliday junction. We show that the enzyme binds remotely to dsDNA and then undergoes 1D diffusion. Upon encountering a four-way junction, a catalytically-impaired mutant remains bound at that point. An active enzyme, however, cleaves the junction after a few seconds. Quantitative analysis provides a comprehensive description of the facilitated diffusion mechanism. We show that the eukaryotic junction-resolving enzyme GEN1 also undergoes facilitated diffusion on dsDNA until it becomes located at a junction, so that the general resolution trajectory is probably applicable to many junction resolving enzymes.
Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance
Authors: Chakravarthy Ankur , Reddin Ian , Henderson Stephen , Dong Cindy , Kirkwood Nerissa , Jeyakumar Maxmilan , Rodriguez Daniela Rothschild , Martinez Natalia Gonzalez , McDermott Jacqueline , Su Xiaoping , Egawa Nagayasau , Fjeldbo Christina S. , Skingen Vilde Eide , Lyng Heidi , Halle Mari Kyllesø , Krakstad Camilla , Soleiman Afschin , Sprung Susanne , Lechner Matt , Ellis Peter J. I. , Wass Mark , Michaelis Martin , Fiegl Heidi , Salvesen Helga , Thomas Gareth J. , Doorbar John , Chester Kerry , Feber Andrew , Fenton Tim R.
Published: October 2022

Human papillomavirus (HPV)-associated cervical cancer is a leading cause of cancer deaths in women. Here we present an integrated multi-omic analysis of 643 cervical squamous cell carcinomas (CSCC, the most common histological variant of cervical cancer), representing patient populations from the USA, Europe and Sub-Saharan Africa and identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 and C2 tumours can be driven by either of the two most common HPV types in cervical cancer (16 and 18) and while HPV16 and HPV18 are overrepresented among C1 and C2 tumours respectively, the prognostic difference between groups is not due to HPV type. C2 tumours, which comprise approximately 20% of CSCCs across these cohorts, display distinct genomic alterations, including loss or mutation of theSTK11tumour suppressor gene, increased expression of several immune checkpoint genes and differences in the tumour immune microenvironment that may explain the shorter survival associated with this group. In conclusion, we identify two therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.
Uncertainty modulates visual maps during noninstrumental information demand
Authors: Li Yvonne , Daddaoua Nabil , Horan Mattias , Foley Nicholas C. , Gottlieb Jacqueline
Published: October 2022

Animals are intrinsically motivated to obtain information independently of instrumental incentives. This motivation depends on two factors: a desire to resolve uncertainty by gathering accurate information and a desire to obtain positively-valenced observations, which predict favorable rather than unfavorable outcomes. To understand the neural mechanisms, we recorded parietal cortical activity implicated in prioritizing stimuli for spatial attention and gaze, in a task in which monkeys were free (but not trained) to obtain information about probabilistic non-contingent rewards. We show that valence and uncertainty independently modulated parietal neuronal activity, and uncertainty but not reward-related enhancement consistently correlated with behavioral sensitivity. The findings suggest uncertainty-driven and valence-driven information demand depend on partially distinct pathways, with the former being consistently related to parietal responses and the latter depending on additional mechanisms implemented in downstream structures.
Prevalence and mechanisms of somatic deletions in single human neurons during normal aging and in DNA repair disorders
Authors: Kim Junho , Huang August Yue , Johnson Shelby L. , Lai Jenny , Isacco Laura , Jeffries Ailsa M. , Miller Michael B. , Lodato Michael A. , Walsh Christopher A. , Lee Eunjung Alice
Published: October 2022

Replication errors and various genotoxins cause DNA double-strand breaks (DSBs) where error-prone repair creates genomic mutations, most frequently focal deletions, and defective repair may lead to neurodegeneration. Despite its pathophysiological importance, the extent to which faulty DSB repair alters the genome, and the mechanisms by which mutations arise, have not been systematically examined reflecting ineffective methods. Here, we develop PhaseDel, a computational method to detect focal deletions and characterize underlying mechanisms in single-cell whole genome sequences (scWGS). We analyzed high-coverage scWGS of 107 single neurons from 18 neurotypical individuals of various ages, and found that somatic deletions increased with age and in highly expressed genes in human brain. Our analysis of 50 single neurons from DNA repair-deficient diseases with progressive neurodegeneration (Cockayne syndrome, Xeroderma pigmentosum, and Ataxia telangiectasia) reveals elevated somatic deletions compared to age-matched controls. Distinctive mechanistic signatures and transcriptional associations suggest roles for somatic deletions in neurodegeneration.
Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue
Authors: Kuijk Ewart , Kranenburg Onno , Cuppen Edwin , Van Hoeck Arne
Published: October 2022

Genome-wide mutation analyses have revealed that specific anti-cancer drugs are highly mutagenic to cancer cells, but the mutational impact of anti-cancer therapies on normal cells is not known. Here, we examine genome-wide somatic mutation patterns in 42 healthy adult stem cells (ASCs) of the colon or the liver from 14 cancer patients (mean of 3.2 ASC per donor) that received systemic chemotherapy and/or local radiotherapy. The platinum-based chemo-drug Oxaliplatin induces on average 535 ± 260 mutations in colon ASC, while 5-FU shows a complete mutagenic absence in most, but not all colon ASCs. In contrast with the colon, normal liver ASCs escape mutagenesis from systemic treatment with Oxaliplatin and 5-FU. Thus, while chemotherapies are highly effective at killing cancer cells, their systemic use also increases the mutational burden of long-lived normal stem cells responsible for tissue renewal thereby increasing the risk for developing second cancers.