bluuebunny/crossref_metadata_2025 huggingface dataset:
Vultures feeding on the dark side: current sanitary regulations may not be enough
Authors: FERNÁNDEZ-GÓMEZ LOLA , CORTÉS-AVIZANDA AINARA , ARRONDO ENEKO , GARCÍA-ALFONSO MARINA , CEBALLOS OLGA , MONTELÍO EUGENIO , DONÁZAR JOSÉ A.
Published: June 2022

It is widely acknowledged that the conservation of vultures, a group of birds threatened worldwide, requires the management of safe, high-quality human subsidies, free of potentially harmful toxic compounds. Additionally, in Europe, the supply of livestock carcasses is subject to current sanitary regulations. It is largely unknown how vultures use sources of food of different abundance, predictability, or different legal status and how individual features shape these preferences. To answer these questions, we took advantage of information yielded by 35 GPS-tagged adult Eurasian Griffon Vultures Gyps fulvus living in a region of northern Spain, which hosts one of the most important European populations. Our results indicated that vultures preferably used predictable feeding sites, such as carcass dumping sites, intensive farms and landfills which together account for the 62% of the observed feeding sites. Less than 10% of all observed sites had permission of authorities for the disposal of the carcasses. Interestingly, sites with large accumulations of carcasses were less used that those with intermediate amounts of food probably because of high intraspecific competition. In addition, sex and breeding status also played a role with males and breeding birds being more prone to visit the studied intensively managed feeding places. This vulture population is heavily dependent on food sources which are not under legal control where the birds could be at risk of intoxication and pathogen acquisition. Hence, current legal scenario allowing farmers to abandon carcasses in their exploitations seems insufficient. The future of vultures in highly anthropized regions is uncertain if interdictory regulations on the abandonment of carcasses of intensive livestock are applied. Additionally, conservation scenarios based on food subsidization must consider the effects of environmental and individual variability. We need science-based strategies ensuring the long-term viability of avian scavenger populations within a scenario of anthropized landscapes and livestock farming intensification.
Demographic composition, post-release and natal dispersal, and breeding success of the reintroduced Oriental Stork Ciconia boyciana
Authors: DEGUCHI TOMOHIRO , OHSAKO YOSHITO , SAGAWA SHIRO , EZAKI YASUO
Published: June 2022

Species restoration through reintroduction and reinforcement is widely considered as an effective method for the conservation of threatened animals. Although these approaches have been increasingly implemented over the last half-century, many attempts have failed. Dispersal behaviour is one of the key factors determining reintroduction success. We reported the demographic composition and dispersal pattern (i.e., post-release and natal dispersal) of a reintroduced Oriental Stork Ciconia boyciana population in Japan and identified the determinants of breeding success in 2005–2019. We hypothesized that one of the key determinants of breeding success is the density-dependent effect through post-release and natal dispersal. The F1 generation occurrence corresponded to two years, F2 to seven, F3 to 11, and F4 to 14 years after initial reintroduction. Wild-born birds accounted for 74% of the reintroduced population at F4 occurrence. Post-release dispersal distances were shorter than natal dispersal. Inter-nest distance was selected as the key factor determining breeding success. These results may have been due to feeding habitat restoration and conspecific interactions. In conclusion, steady recruitment to the next generation is thought to be due to a moderate natal dispersal and the subsequent low breeding density of wild-born birds.
Development of a Scale for Assessing Basic Psychotherapeutic Skills
Authors: Kühne Franziska , Heinze Peter Eric , Ay-Bryson Destina Sevde , Maaß Ulrike , Weck and Florian
Published: June 2022

Abstract. Background: Well-established scales for the observation-based assessment of psychotherapy competence encompass multiple domains, require extensive rater training, and are rather cost-intensive. Objective: To develop a comprehensive but easy-to-administer instrument for the observation-based assessment of basic communication and counseling skills in both real and simulated patient encounters, the Clinical Communication Skills Scale (CCSS). Methods: We investigated the content validity and applicability of this scale. We then presented videos of simulated therapy sessions conducted by a competent vs. noncompetent therapist online to N = 209 laypersons and psychology students. Results: Results suggested a one-factorial solution. Internal consistency was excellent ( α = .94). For most aspects, convergent validity with established scales was moderate to high. The CCSS effectively differentiated between both levels of skill. Conclusions: The CCSS appears to be a feasible, reliable, and valid instrument. Nonetheless, its psychometric criteria should be investigated further in clinical samples, with licensed therapists, and in other languages.
Ist der Einsatz simulierter Patient_innen zum Erwerb psychotherapeutischer Fertigkeiten praktikabel?
Authors: Kühne Franziska , Maaß Ulrike , Stephan Isabell , Weck Florian
Published: June 2022

Zusammenfassung. Theoretischer Hintergrund: Da der Kompetenzerwerb in der Psychotherapieausbildung maßgeblich durch Üben und systematisches Feedback bestimmt wird, wurde eine Online-Lehrveranstaltung entwickelt, in der erfahrungsbasiertes Lernen mit Simulationspatient_innen (SP) und strukturiertes Feedback kombiniert wurden. Fragestellung: Ziel der Studie war die qualitative und quantitative Evaluation der Lehrveranstaltung. Methode: Zunächst wurden halbstandardisierte Interviews mit Seminarteilnehmer_innen, SP und der Supervisorin durchgeführt und inhaltsanalytisch ausgewertet. Außerdem wurden die Gesprächsführungsfertigkeiten der Student_innen (aus Sicht einer Supervisorin) und die therapeutische Selbstwirksamkeit (Selbstbeurteilung) im Seminarverlauf erhoben. Ergebnisse: Zwischen N = 13 und 15 Masterstudent_innen der Klinischen Psychologie, die beiden SP und die Supervisorin nahmen an Begleitstudie und Interviews teil. Die Student_innen schätzten v. a. den Praxisbezug des Seminars, wünschten sich mehr Interaktionen mit SP und noch häufigeres Feedback. Das Onlineformat wurde als Übergangslösung wahrgenommen. Gesprächsführungsfertigkeiten und therapeutische Selbstwirksamkeit nahmen signifikant zu. Schlussfolgerungen: Erfahrungsbasiertes Lernen kann mit SP und Feedback praktikabel umgesetzt werden, allerdings sollten Präsenzrollenspiele zumindest ergänzend angeboten werden.
The Nature of Word Associations in Sentence Contexts
Authors: Planchuelo Clara , Buades-Sitjar Francisco , Hinojosa José Antonio , Duñabeitia Jon Andoni
Published: June 2022

Abstract. How words are interrelated in the human mind is a scientific topic on which there is still no consensus, with different views on how word co-occurrence and semantic relatedness mediate word association. Recent research has shown that lexical associations are strongly predicted by the similarity of those words in terms of valence, arousal, and concreteness ratings. In the current study, we aimed at extending these results to more complex and realistic linguistic scenarios, since human communication is not done with word pairs, but rather through sentences. Hence, the aim of the current study was to verify whether valence, arousal, and concreteness also articulate sentence-level lexical representations. To this end, 32 native Spanish speakers were given cue words and asked to use them in sentences that would provide a meaningful context. The content words of the written sentences were then analyzed. Our results showed that the emotional dimensions (valence and arousal) and concreteness values of the cue words effectively predicted the same values of said dimensions of their sentences’ words. In sum, the similarity in the emotional dimensions and concreteness are crucial mechanisms behind word association in the human mind.
Forest Resource Availability After Nuclear War or Other Sun‐Blocking Catastrophes
Authors: Winstead Daniel Jefferson , Jacobson Michael Gregory
Published: June 2022

A global, sun‐blocking catastrophe like nuclear war, an asteroid strike, or a super volcano eruption spells disaster for most aspects of life as we know it. There have been many studies on how differing magnitudes of sun‐blocking catastrophes would affect the global climate, and many mention the effects of this cold, dark climate on forests and cropping systems. However, few studies have solely focused on the effects of nuclear winter on forests in terms of food, resources, and decomposition. Forests already provide over a billion people with food and fuel for their livelihoods. In this review, we connect how prehistoric catastrophes affected the world's forests to how a current‐day catastrophe may affect forest health, forest resource availability, and wood decomposition rates. We briefly discuss how forest resources may be used in this post‐catastrophe climate for food and fuel in an energy and fuel‐depleted world. We use this information to make policy and education suggestions to prepare for future catastrophes, build resilience from smaller local disasters, prepare for the many effects of climate change, and discourage nuclear weapon stockpiles.
Terahertz Wave Propagation Characteristics on Rough Surfaces Based on Full‐Wave Simulations
Authors: Xie Pengxiang , Guan Ke , He Danping , Yi Haofan , Dou Jianwu , Zhong Zhangdui
Published: June 2022

Terahertz (THz) communications are considered as a critical technology for the future wireless communication. The THz band (0.1–10 THz) offers ultra‐wide bandwidths and promises to satisfy the need for ultra‐high‐speed wireless communication. Although propagation characterization is necessary for the THz system design and validation, the response mechanism between the surface roughness and the THz wave is rarely studied. According to the Rayleigh Criterion, most surfaces in a physical environment may be considered to be rough. Scattering on rough surfaces will play a significant role in the THz propagation. Due to the difficulty of practical measurements at the THz band, we use a full‐wave simulation method to study the propagation characteristics of scattering on rough surfaces. First, the Monte Carlo method is used to model rough surfaces with different root‐mean‐squared heights δ and correlation lengths l. Then, with full‐wave simulations, frequency dependency, incident angle dependency, material dependency, and surface size dependency are discussed. By changing the roughness of surfaces, scattering on different rough surfaces at 300 GHz are simulated. Based on a large number of simulation results, we investigate the effect of δ and l on scattering on rough surfaces. Afterward, the cross‐polarization discrimination of each case is analyzed and counted to evaluate the depolarization effect. This study shows that scattering can become a prominent propagation mechanism with the growth of roughness. Besides, the depolarization effect becomes much more severe for a rougher surface. Studying THz propagation characteristics on rough surfaces is critical to accurate THz channel modeling, which further supports the design and deployment of THz communication systems.
Intention Versus Action: Household Adoption of Best Management Practices for Water Quality
Authors: Fleming Patrick M. , Savchenko Olesya M.
Published: June 2022

Adoption rates of household water quality management practices remain extremely low, despite survey evidence indicating substantial willingness to adopt. Using a quasi‐experimental survey design, we investigate the presence of hypothetical bias in household stormwater surveys and compare the effectiveness of two ex‐ante bias mitigation techniques: survey consequentiality and a cheap talk script. Households facing survey consequentiality are willing to pay 38% less for stormwater practices compared with the control. This results in expected adoption rates that are up to 60% lower than those indicated by responses in the control group. In contrast the cheap talk script did not significantly alter willingness to pay for any management practice analyzed. After accounting for hypothetical bias, local policy goals for rain garden adoption imply a household subsidy program that consumes almost three times the budget of that implied by survey responses without a consequentiality reminder.
Channel Conveyance Variability can Influence Flood Risk as Much as Streamflow Variability in Western Washington State
Authors: Ahrendt Shelby , Horner‐Devine Alexander R. , Collins Brian D. , Morgan Jacob A. , Istanbulluoglu Erkan
Published: June 2022

Changes in the severity and likelihood of flooding events are typically associated with changes in the intensity and frequency of streamflows, but temporal adjustments in a river's conveyance capacity can also contribute to shifts in flood hazard. To assess the relative importance of channel conveyance to flood hazard, we compare variations in channel conveyance to variations in the flow magnitude of moderate (1.2 years) floods at 50 river gauges in western Washington State between 1930 and 2020. In unregulated rivers, moderate floods have increased across the region, but in regulated rivers this trend is suppressed and in some cases reversed. Variations in channel conveyance are ubiquitous, but the magnitude and timing of adjustments are not regionally uniform. At 40% of gages, conveyance changes steadily and gradually. More often, however, conveyance variability is nonlinear, consisting of multidecadal oscillations (36% of gages), rapid changes due to unusually large sediment‐supply events (14% of gages), and increases or decreases to conveyance following flow regulation (10% of gages). The relative importance of conveyance variability for flood risk depends on the mode of adjustment; in certain locations with historic landslides, extreme floods, and flow regulation, the influence of conveyance changes on flood risk matches or exceeds that of streamflow at the same site. Flood hazard management would benefit from incorporating historic long‐term and short‐term conveyance changes in predictions of future flood hazard variability.
Predicting the future of neuroimaging predictive models in mental health
Authors: Tejavibulya Link , Rolison Max , Gao Siyuan , Liang Qinghao , Peterson Hannah , Dadashkarimi Javid , Farruggia Michael C. , Hahn C. Alice , Noble Stephanie , Lichenstein Sarah D. , Pollatou Angeliki , Dufford Alexander J. , Scheinost Dustin
Published: June 2022

Predictive modeling using neuroimaging data has the potential to improve our understanding of the neurobiology underlying psychiatric disorders and putatively information interventions. Accordingly, there is a plethora of literature reviewing published studies, the mathematics underlying machine learning, and the best practices for using these approaches. As our knowledge of mental health and machine learning continue to evolve, we instead aim to look forward and “predict” topics that we believe will be important in current and future studies. Some of the most discussed topics in machine learning, such as bias and fairness, the handling of dirty data, and interpretable models, may be less familiar to the broader community using neuroimaging-based predictive modeling in psychiatry. In a similar vein, transdiagnostic research and targeting brain-based features for psychiatric intervention are modern topics in psychiatry that predictive models are well-suited to tackle. In this work, we target an audience who is a researcher familiar with the fundamental procedures of machine learning and who wishes to increase their knowledge of ongoing topics in the field. We aim to accelerate the utility and applications of neuroimaging-based predictive models for psychiatric research by highlighting and considering these topics. Furthermore, though not a focus, these ideas generalize to neuroimaging-based predictive modeling in other clinical neurosciences and predictive modeling with different data types (e.g., digital health data).
Chimeric cerebral organoids reveal the essentials of neuronal and astrocytic APOE4 for Alzheimer’s tau pathology
Authors: Huang Shichao , Zhang Zhen , Cao Junwei , Yu Yongchun , Pei Gang
Published: June 2022

The apolipoprotein E4 (APOE4) genotype is one of the strongest genetic risk factors for Alzheimer’s disease (AD), and is generally believed to cause widespread pathological alterations in various types of brain cells. Here, we developed a novel engineering method of creating the chimeric human cerebral organoids (chCOs) to assess the differential roles of APOE4 in neurons and astrocytes. First, the astrogenic factors NFIB and SOX9 were introduced into induced pluripotent stem cells (iPSCs) to accelerate the induction of astrocytes. Then the above induced iPSCs were mixed and cocultured with noninfected iPSCs under the standard culturing condition of cerebral organoids. As anticipated, the functional astrocytes were detected as early as 45 days, and it helped more neurons matured in chCOs in comparation of the control human cerebral organoids (hCOs). More interestingly, this method enabled us to generate chCOs containing neurons and astrocytes with different genotypes, namely APOE3 or APOE4. Then, it was found in chCOs that astrocytic APOE4 already significantly promoted lipid droplet formation and cholesterol accumulation in neurons while both astrocytic and neuronal APOE4 contributed to the maximum effect. Most notably, we observed that the co-occurrence of astrocytic and neuronal APOE4 were required to elevate neuronal phosphorylated tau levels in chCOs while Aβ levels were increased in chCOs with neuronal APOE4. Altogether, our results not only revealed the essence of both neuronal and astrocytic APOE4 for tau pathology, but also suggested chCOs as a valuable pathological model for AD research and drug discovery.
Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population
Authors: Thomas Taylor R. , Koomar Tanner , Casten Lucas G. , Tener Ashton J. , Bahl Ethan , Michaelson Jacob J.
Published: June 2022

The complexity of autism’s phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is undetermined if autistic symptom domain severity underlying this heterogeneity is heritable and pleiotropic with other psychiatric and behavior traits in the same manner as autism case-control status. InN = 6064 autistic children in the SPARK cohort, we investigated the common genetic properties of twelve subscales from three clinical autism instruments measuring autistic traits: the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), and the Developmental Coordination Disorder Questionnaire (DCDQ). Educational attainment polygenic scores (PGS) were significantly negatively correlated with eleven subscales, while ADHD and major depression PGS were positively correlated with ten and eight of the autism subscales, respectively. Loneliness and neuroticism PGS were also positively correlated with many subscales. Significant PGS by sex interactions were found—surprisingly, the autism case-control PGS was negatively correlated in females and had no strong correlation in males. SNP-heritability of the DCDQ subscales ranged from 0.04 to 0.08, RBS-R subscales ranged from 0.09 to 0.24, and SCQ subscales ranged from 0 to 0.12. GWAS in SPARK followed by estimation of polygenic scores (PGS) in the typically-developing ABCD cohort (N = 5285), revealed significant associations of RBS-R subscale PGS with autism-related behavioral traits, with several subscale PGS more strongly correlated than the autism case-control PGS. Overall, our analyses suggest that the clinical autism subscale traits show variability in SNP-heritability, PGS associations, and significant PGS by sex interactions, underscoring the heterogeneity in autistic traits at a genetic level. Furthermore, of the three instruments investigated, the RBS-R shows the greatest evidence of genetic signal in both (1) autistic samples (greater heritability) and (2) general population samples (strongest PGS associations).
Prevalence of Molar-incisor hypomineralization in Iranian children – A systematic review and narrative synthesis
Authors: Afshari Elham , Dehghan Farzaneh , Vakili Mohammad Ali , Abbasi Marzieh
Published: June 2022

Introduction

Molar-incisor hypomineralization is a developmental defect of enamel with clinical features vary from demarcated opacities to severe tissue breakdown which calls for considerable preventive and interceptive measures. The aim of this article was to systematically review the literature on the prevalence of MIH in Iran and highlight the condition in Iranian children.

Materials and Methods

A systematic search of literature was conducted in Scopus, Pubmed, Ovid, Embase, Web of Science, and Google-Scholar as well as national Iranian database and digital archives of dental schools from the beginning of 2000 to the end of 2021 for published and unpublished studies. Data from cross-sectional, cohort, and case-control studies on prevalence of molar-incisor hypomineralization among 6–13-year-old children was gathered, using the following MeSH terms and keywords and their Persian equivalents: Prevalence, Hypomineralisation, Hypomineralization, MIH, “molar incisor”, “molar-incisor”, “cheese molars”, “Hypomineralised first permanent molars”, “Hypomineralized first permanent molars”, “developmental defects of enamel”, “enamel developmental defects”, Iran*. Methodological quality and the risk of bias of quantitative studies was assessed using a modified version of Newcastle-Ottawa Scale. Due to the considerable clinical and statistical heterogeneity of the included studies, pooling of data through meta-analysis was not possible. Therefore, a descriptive synthesis of data was performed.

Results

Fifteen cross-sectional studies with a total number of 12011 participants were included in the systematic review. The prevalence of MIH ranged from 5.1% to 25.6%. All of the included studies were at a moderate risk of bias (NOS of 4-6). The lowest prevalence of MIH was reported in Kerman (5.14%) and the highest in Tehran (25.6%). Substantial methodological, clinical and statistical heterogeneity was observed.

Conclusion

This is the first study to systematically review the available literature on MIH prevalence in Iran. However, the present review has some limitations such as limited number of included studies, large heterogeneity of the research, and moderate quality of included studies. Further high-quality research is warranted.
Histone H3K36me2 demethylase KDM2A promotes bladder cancer progression through epigenetically silencing RARRES3
Authors: Lu Bing , Wei Jiatian , Zhou Houhong , Chen Jie , Li Yuqing , Ye Liefu , Zhao Wei , Wu Song
Published: June 2022

Epigenetic dysregulation contributes to bladder cancer tumorigenesis. H3K36me2 demethylase KDM2A functions as an important epigenetic regulator of cell fate in many types of tumors. However, its role in bladder cancer remains unknown. Here, we revealed a positive correlation between KDM2A gene copy number gain and upregulation of KDM2A mRNA expression in bladder cancer. Moreover, a super-enhancer (SE) driving KDM2A transcription was found in high-grade bladder cancer, resulting in a significantly higher expression of KDM2A mRNA compared to that in low-grade bladder tumors. KDM2A knockdown (KD) decreased the proliferation, invasion, and spheroid formation of high-grade bladder cancer cells and inhibited tumor growth in mouse xenograft models. Furthermore, we identified RARRES3 as a key KDM2A target gene. KDM2A suppresses RARRES3 expression via demethylation of H3K36me2 in the RARRES3 promoter. Intriguingly, RARRES3 KD attenuated the inhibitory effects of KDM2A depletion on the malignant phenotypes of high-grade bladder cancer cells. The combination of the KDM2A inhibitor IOX1 and the RARRES3 agonist all-trans retinoic acid (ATRA) synergistically inhibited the proliferation of high-grade bladder cancer cells, suggesting that the KDM2A/RARRES3 axis may be a promising therapeutic target for the treatment of high-grade bladder cancer.
Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery
Authors: Hatano Tomoyuki , Palani Saravanan , Papatziamou Dimitra , Salzer Ralf , Souza Diorge P. , Tamarit Daniel , Makwana Mehul , Potter Antonia , Haig Alexandra , Xu Wenjue , Townsend David , Rochester David , Bellini Dom , Hussain Hamdi M. A. , Ettema Thijs J. G. , Löwe Jan , Baum Buzz , Robinson Nicholas P. , Balasubramanian Mohan
Published: June 2022

The ESCRT machinery, comprising of multiple proteins and subcomplexes, is crucial for membrane remodelling in eukaryotic cells, in processes that include ubiquitin-mediated multivesicular body formation, membrane repair, cytokinetic abscission, and virus exit from host cells. This ESCRT system appears to have simpler, ancient origins, since many archaeal species possess homologues of ESCRT-III and Vps4, the components that execute the final membrane scission reaction, where they have been shown to play roles in cytokinesis, extracellular vesicle formation and viral egress. Remarkably, metagenome assemblies of Asgard archaea, the closest known living relatives of eukaryotes, were recently shown to encode homologues of the entire cascade involved in ubiquitin-mediated membrane remodelling, including ubiquitin itself, components of the ESCRT-I and ESCRT-II subcomplexes, and ESCRT-III and Vps4. Here, we explore the phylogeny, structure, and biochemistry of Asgard homologues of the ESCRT machinery and the associated ubiquitylation system. We provide evidence for the ESCRT-I and ESCRT-II subcomplexes being involved in ubiquitin-directed recruitment of ESCRT-III, as it is in eukaryotes. Taken together, our analyses suggest a pre-eukaryotic origin for the ubiquitin-coupled ESCRT system and a likely path of ESCRT evolution via a series of gene duplication and diversification events.
Plasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa
Authors: Silva Joana C. , Dwivedi Ankit , Moser Kara A. , Sissoko Mahamadou S. , Epstein Judith E. , Healy Sara A. , Lyke Kirsten E. , Mordmüller Benjamin , Kremsner Peter G. , Duffy Patrick E. , Murshedkar Tooba , Sim B. Kim Lee , Richie Thomas L. , Hoffman Stephen L.
Published: June 2022

Controlled human malaria infection (CHMI) has supported Plasmodium falciparum (Pf) malaria vaccine development by providing preliminary estimates of vaccine efficacy (VE). Because CHMIs generally use Pf strains similar to vaccine strains, VE against antigenically heterogeneous Pf in the field has been required to establish VE. We increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African parasite (PfNF54) in our PfSPZ vaccines. Using two regimens to identically immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than VE against CHMI at 24 weeks in the US. To explain this finding, here we quantify differences in the genome, proteome, and predicted CD8 T cell epitopes of PfNF54 relative to 704 Pf isolates from Africa and Pf7G8. We show that Pf7G8 is more distant from PfNF54 than any African isolates tested. We propose VE against Pf7G8 CHMI for providing pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from the Pf vaccine strain makes it a stringent surrogate for Pf parasites in Africa.
High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells
Authors: Boya Mert , Ozkaya-Ahmadov Tevhide , Swain Brandi E. , Chu Chia-Heng , Asmare Norh , Civelekoglu Ozgun , Liu Ruxiu , Lee Dohwan , Tobia Sherry , Biliya Shweta , McDonald L. DeEtte , Nazha Bassel , Kucuk Omer , Sanda Martin G. , Benigno Benedict B. , Moreno Carlos S. , Bilen Mehmet A. , McDonald John F. , Sarioglu A. Fatih
Published: June 2022

Extremely rare circulating tumor cell (CTC) clusters are both increasingly appreciated as highly metastatic precursors and virtually unexplored. Technologies are primarily designed to detect single CTCs and often fail to account for the fragility of clusters or to leverage cluster-specific markers for higher sensitivity. Meanwhile, the few technologies targeting CTC clusters lack scalability. Here, we introduce the Cluster-Wells, which combines the speed and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips. The >100,000 microwells in the Cluster-Wells physically arrest CTC clusters in unprocessed whole blood, gently isolating virtually all clusters at a throughput of >25 mL/h, and allow viable clusters to be retrieved from the device. Using the Cluster-Wells, we isolated CTC clusters ranging from 2 to 100+ cells from prostate and ovarian cancer patients and analyzed a subset using RNA sequencing. Routine isolation of CTC clusters will democratize research on their utility in managing cancer.
Cellulose photonic pigments
Authors: Parker Richard M. , Zhao Tianheng H. , Frka-Petesic Bruno , Vignolini Silvia
Published: June 2022

When pursuing sustainable approaches to fabricate photonic structures, nature can be used as a source of inspiration for both the nanoarchitecture and the constituent materials. Although several biomaterials have been promised as suitable candidates for photonic materials and pigments, their fabrication processes have been limited to the small to medium-scale production of films. Here, by employing a substrate-free process, structurally coloured microparticles are produced via the confined self-assembly of a cholesteric cellulose nanocrystal (CNC) suspension within emulsified microdroplets. Upon drying, the droplets undergo multiple buckling events, which allow for greater contraction of the nanostructure than predicted for a spherical geometry. This buckling, combined with a solvent or thermal post-treatment, enables the production of dispersions of vibrant red, green, and blue cellulose photonic pigments. The hierarchical structure of these pigments enables the deposition of coatings with angular independent colour, offering a consistent visual appearance across a wide range of viewing angles.
A proteogenomic signature of age-related macular degeneration in blood
Authors: Emilsson Valur , Gudmundsson Elias F. , Jonmundsson Thorarinn , Jonsson Brynjolfur G. , Twarog Michael , Gudmundsdottir Valborg , Li Zhiguang , Finkel Nancy , Poor Stephen , Liu Xin , Esterberg Robert , Zhang Yiyun , Jose Sandra , Huang Chia-Ling , Liao Sha-Mei , Loureiro Joseph , Zhang Qin , Grosskreutz Cynthia L. , Nguyen Andrew A. , Huang Qian , Leehy Barrett , Pitts Rebecca , Aspelund Thor , Lamb John R. , Jonasson Fridbert , Launer Lenore J. , Cotch Mary Frances , Jennings Lori L. , Gudnason Vilmundur , Walshe Tony E.
Published: June 2022

Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.
Defect engineering of layered double hydroxide nanosheets as inorganic photosensitizers for NIR-III photodynamic cancer therapy
Authors: Shen Weicheng , Hu Tingting , Liu Xueyan , Zha Jiajia , Meng Fanqi , Wu Zhikang , Cui Zhuolin , Yang Yu , Li Hai , Zhang Qinghua , Gu Lin , Liang Ruizheng , Tan Chaoliang
Published: June 2022

Although two-dimensional (2D) layered double hydroxides (LDHs) have been widely used as efficient nanoagents for biological diagnosis and treatment, they have been found to be inert as photosensitizers (PSs) for photodynamic therapy (PDT). Herein, we report the defect engineering of ultrathin 2D CoMo-LDH and NiMo-LDH nanosheets as highly active inorganic PSs for PDT in the third near-infrared (NIR-III) window. Hydrothermal-synthesized 2D CoMo-LDH and NiMo-LDH nanosheets are etched via a simple acid treatment to obtain defect-rich CoMo-LDH and NiMo-LDH nanosheets. Importantly, the defect-rich CoMo-LDH nanosheets exhibit much higher activity (~97 times) for generation of reactive oxygen species than that of the pristine CoMo-LDH nanosheets under a NIR-III 1567 nm laser irradiation. Therefore, after modification with polyethylene glycol, the defect-rich CoMo-LDH nanosheets can be used as an efficient inorganic PS for PDT to efficiently induce cancer cells apoptosis in vitro and eradicate tumors in vivo under 1567 nm laser irradiation.
Compact IF2 allows initiator tRNA accommodation into the P site and gates the ribosome to elongation
Authors: Basu Ritwika S. , Sherman Michael B. , Gagnon Matthieu G.
Published: June 2022

During translation initiation, initiation factor 2 (IF2) holds initiator transfer RNA (fMet-tRNAifMet) in a specific orientation in the peptidyl (P) site of the ribosome. Upon subunit joining IF2 hydrolyzes GTP and, concomitant with inorganic phosphate (Pi) release, changes conformation facilitating fMet-tRNAifMet accommodation into the P site and transition of the 70 S ribosome initiation complex (70S-IC) to an elongation-competent ribosome. The mechanism by which IF2 separates from initiator tRNA at the end of translation initiation remains elusive. Here, we report cryo-electron microscopy (cryo-EM) structures of the 70S-IC from Pseudomonas aeruginosa bound to compact IF2-GDP and initiator tRNA. Relative to GTP-bound IF2, rotation of the switch 2 α-helix in the G-domain bound to GDP unlocks a cascade of large-domain movements in IF2 that propagate to the distal tRNA-binding domain C2. The C2-domain relocates 35 angstroms away from tRNA, explaining how IF2 makes way for fMet-tRNAifMet accommodation into the P site. Our findings provide the basis by which IF2 gates the ribosome to the elongation phase.
Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction
Authors: Zijlmans Dick W. , Talon Irene , Verhelst Sigrid , Bendall Adam , Van Nerum Karlien , Javali Alok , Malcolm Andrew A. , van Knippenberg Sam S. F. A. , Biggins Laura , To San Kit , Janiszewski Adrian , Admiraal Danielle , Knops Ruth , Corthout Nikky , Balaton Bradley P. , Georgolopoulos Grigorios , Panda Amitesh , Bhanu Natarajan V. , Collier Amanda J. , Fabian Charlene , Allsop Ryan N. , Chappell Joel , Pham Thi Xuan Ai , Oberhuemer Michael , Ertekin Cankat , Vanheer Lotte , Athanasouli Paraskevi , Lluis Frederic , Deforce Dieter , Jansen Joop H. , Garcia Benjamin A. , Vermeulen Michiel , Rivron Nicolas , Dhaenens Maarten , Marks Hendrik , Rugg-Gunn Peter J. , Pasque Vincent
Published: June 2022

Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stem cells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition of PRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
Lower oceanic crust formed by in situ melt crystallization revealed by seismic layering
Authors: Guo Peng , Singh Satish C. , Vaddineni Venkata A. , Grevemeyer Ingo , Saygin Erdinc
Published: June 2022

Oceanic crust forms at mid-ocean spreading centres through a combination of magmatic and tectonic processes, with the magmatic processes creating two distinct layers: the upper and the lower crust. While the upper crust is known to form from lava flows and basaltic dykes based on geophysical and drilling results, the formation of the gabbroic lower crust is still debated. Here we perform a full waveform inversion of wide-angle seismic data from relatively young (7–12-Myr-old) crust formed at the slow-spreading Mid-Atlantic Ridge. The seismic velocity model reveals alternating, 400–500 m thick, high- and low-velocity layers with ±200 m s−1 velocity variations, below ~2 km from the oceanic basement. The uppermost low-velocity layer is consistent with hydrothermal alteration, defining the base of extensive hydrothermal circulation near the ridge axis. The underlying layering supports that the lower crust is formed through the intrusion of melt as sills at different depths, which cool and crystallize in situ. The layering extends up to 5–15 km distance along the seismic profile, covering 300,000–800,000 years, suggesting that this form of lower crustal accretion is a stable process.
A database of anti-coronavirus peptides
Authors: Zhang Qianyue , Chen Xue , Li Bowen , Lu Chunying , Yang Shanshan , Long Jinjin , Chen Heng , Huang Jian , He Bifang
Published: June 2022

Since 2019, the novel coronavirus (SARS-COV-2) disease (COVID-19) has caused a worldwide epidemic. Anti-coronavirus peptides (ACovPs), a type of antimicrobial peptides (AMPs), have demonstrated excellent inhibitory effects on coronaviruses. However, state-of-the-art AMP databases contain only a small number of ACovPs. Additionally, the fields of these databases are not uniform, and the units or evaluation standards of the same field are inconsistent. Most of these databases have not included the target domains of ACovPs and description of in vitro and in vivo assays to measure the inhibitory effects of ACovPs. Here, we present a database focused on ACovPs (ACovPepDB), which contains comprehensive and precise ACovPs information of 518 entries with 214 unique ACovPs manually collected from public databases and published peer-reviewed articles. We believe that ACovPepDB is of great significance for facilitating the development of new peptides and improving treatment for coronavirus infection. The database will become a portal for ACovPs and guide and help researchers perform further studies. The ACovPepDB is available at http://i.uestc.edu.cn/ACovPepDB/.
A digital assay for programmed death-ligand 1 (22C3) quantification combined with immune cell recognition algorithms in non-small cell lung cancer
Authors: Paces Will , Ergon Elliott , Bueche Elizabeth , Young G. Dave , Adisetiyo Vitria , Luengo Cris , James Meredith , Caldwell Charles , Miller Dannah , Wambaugh Morgan , Metcalf Geoffrey , Gianani Roberto
Published: June 2022

PD-L1 (22C3) checkpoint inhibitor therapy represents a mainstay of modern cancer immunotherapy for non-small cell lung cancer (NSCLC). In vitro diagnostic (IVD) PD-L1 antibody staining is widely used to predict clinical intervention efficacy. However, pathologist interpretation of this assay is cumbersome and variable, resulting in poor positive predictive value concerning patient therapy response. To address this, we developed a digital assay (DA) termed Tissue Insight (TI) 22C3 NSCLC, for the quantification of PD-L1 in NSCLC tissues, including digital recognition of macrophages and lymphocytes. We completed clinical validation of this digital image analysis solution in 66 NSCLC patient samples, followed by concordance studies (comparison of PD-L1 manual and digital scores) in an additional 99 patient samples. We then combined this DA with three distinct immune cell recognition algorithms for detecting tissue macrophages, alveolar macrophages, and lymphocytes to aid in sample interpretation. Our PD-L1 (22C3) DA was successfully validated and had a scoring agreement (digital to manual) higher than the inter-pathologist scoring. Furthermore, the number of algorithm-identified immune cells showed significant correlation when compared with those identified by immunohistochemistry in serial sections stained by double immunofluorescence. Here, we demonstrated that TI 22C3 NSCLC DA yields comparable results to pathologist interpretation while eliminating the intra- and inter-pathologist variability associated with manual scoring while providing characterization of the immune microenvironment, which can aid in clinical treatment decisions.
Character gated recurrent neural networks for Arabic sentiment analysis
Authors: Omara Eslam , Mousa Mervat , Ismail Nabil
Published: June 2022

Sentiment analysis is a Natural Language Processing (NLP) task concerned with opinions, attitudes, emotions, and feelings. It applies NLP techniques for identifying and detecting personal information from opinionated text. Sentiment analysis deduces the author's perspective regarding a topic and classifies the attitude polarity as positive, negative, or neutral. In the meantime, deep architectures applied to NLP reported a noticeable breakthrough in performance compared to traditional approaches. The outstanding performance of deep architectures is related to their capability to disclose, differentiate and discriminate features captured from large datasets. Recurrent neural networks (RNNs) and their variants Long-Short Term Memory (LSTM), Gated Recurrent Unit (GRU), Bi-directional Long-Short Term Memory (Bi-LSTM), and Bi-directional Gated Recurrent Unit (Bi-GRU) architectures are robust at processing sequential data. They are commonly used for NLP applications as they—unlike RNNs—can combat vanishing and exploding gradients. Also, Convolution Neural Networks (CNNs) were efficiently applied for implicitly detecting features in NLP tasks. In the proposed work, different deep learning architectures composed of LSTM, GRU, Bi-LSTM, and Bi-GRU are used and compared for Arabic sentiment analysis performance improvement. The models are implemented and tested based on the character representation of opinion entries. Moreover, deep hybrid models that combine multiple layers of CNN with LSTM, GRU, Bi-LSTM, and Bi-GRU are also tested. Two datasets are used for the models implementation; the first is a hybrid combined dataset, and the second is the Book Review Arabic Dataset (BRAD). The proposed application proves that character representation can capture morphological and semantic features, and hence it can be employed for text representation in different Arabic language understanding and processing tasks.
Association of weight change patterns across adulthood with incident asthma: a retrospective cohort study
Authors: Zhang Wei , Du Jie , Wang Shaochun , Ma Huihui
Published: June 2022

This study aimed to investigate the relationship between weight change patterns across adulthood and the risk of incident asthma later in life using data from the National Health and Nutrition Examination Survey (NHANES) 2001–2018. In this retrospective cohort study, asthma was defined by self-report questionnaires, and age at diagnosis was used to estimate the time of asthma onset. Based on BMI at 25 years old (young adulthood) and BMI at 10 years before the survey (middle adulthood), patterns of weight change were divided into five categories including stable normal, non-obese to obese, obese to non-obese, maximum overweight and stable obese. A total of 27,359 participants (female 13,582, 49.6%) were enrolled in this study and during a mean follow-up of 9.8 years, 1035 subjects occurred asthma. After adjusting for age, gender, race, education, family income and smoking status, participants changing from non-obese to obese, stable obese had significantly higher risks of incident asthma than those with normal weight during adulthood (HR1.70, 95% CI 1.35–2.15, P < 0.0001; HR 1.66, 95% CI 1.21–2.19 P = 0.0019, respectively). The findings suggested that maintaining normal weight during adulthood may be important for preventing incident asthma in later life.
Pricing risk-based catastrophe bonds for earthquakes at an urban scale
Authors: Mistry Harsh K. , Lombardi Domenico
Published: June 2022

Catastrophe risk-based bonds are used by governments, financial institutions and (re)insurers to transfer the financial risk associated to the occurrence of catastrophic events, such as earthquakes, to the capital market. In this study, we show how municipalities prone to earthquakes can use this type of insurance-linked security to protect their building stock and communities from economic losses, and ultimately increase their earthquake resilience. We consider Benevento, a middle-sized historical town in southern Italy, as a case study, although the same approach is applicable to other urban areas in seismically active regions. One of the crucial steps in pricing catastrophe bonds is the computation of aggregate losses. We compute direct economic losses for each exposed asset based on high spatial resolution hazard and exposure models. Finally, we use the simulated loss data to price two types of catastrophe bonds (zero-coupon and coupon bonds) for different thresholds and maturity times. Although the present application focuses on earthquakes, the framework can potentially be applied to other natural disasters, such as hurricanes, floods, and other extreme weather events.
Immunotherapeutic effects of recombinant colorectal cancer antigen produced in tomato fruits
Authors: Park Se Hee , Ji Kon-Young , Park Seo Young , Kim Hyun Min , Ma Sang Hoon , Do Ju Hui , Kang Hyuno , Kang Hyung Sik , Oh Doo-Byoung , Shim Jae Sung , Joung Young Hee
Published: June 2022

The production of pharmacological vaccines in plants has been an important goal in the field of plant biotechnology. GA733-2, the protein that is also known as colorectal carcinoma (CRC)-associated antigen, is a strong candidate to produce a colorectal cancer vaccine. Tomato is the one of the major targets for production of an edible vaccine, as tomato is a fruit consumed in fresh form. It also contains high content of vitamins that aid activation of immune response. In order to develop an edible colorectal cancer vaccine, the transgene rGA733-Fc that encodes a fusion protein of GA733-2, the fragment crystallizable (Fc) domain, and the ER retention motif (rGA733-Fc) was introduced into tomato plants (Solanumlycopersicum cv. Micro-Tom). The transgenic plants producing rGA733-Fc (rGA733-FcOX) protein were screened based on stable integration of transgene expression cassette and expression level of rGA733-Fc protein. Further glycosylation pattern analysis revealed that plant derived rGA733-Fc protein contains an oligomannose glycan structure, which is a typical glycosylation pattern found on ER-processing proteins. The red fruits of rGA733-FcOX transgenic tomato plants containing approximately 270 ng/g FW of rGA733-Fc protein were orally administered to C57BL/6 mice. Oral administration of tomato fruits of the rGA733-Fc expressing transgenic plants delayed colorectal cancer growth and stimulated immune responses compared to oral administration of tomato fruits of the h-Fc expressing transgenic plants in the C57BL/6J mice. This is the first study showing the possibility of producing an edible colorectal cancer vaccine using tomato plants. This research would be helpful for development of plant-derived cancer edible vaccines.