bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses
Authors: Beumer Joep , Geurts Maarten H. , Lamers Mart M. , Puschhof Jens , Zhang Jingshu , van der Vaart Jelte , Mykytyn Anna Z. , Breugem Tim I. , Riesebosch Samra , Schipper Debby , van den Doel Petra B. , Lau Wim de , Pleguezuelos-Manzano Cayetano , Busslinger Georg , Haagmans Bart L. , Clevers Hans 
Published: May 2021

AbstractRapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids (IOs) are increasingly used to model human disease and are amenable to genetic engineering. To discern which host factors are reliable anti-coronavirus therapeutic targets, we generate mutant clonal IOs for 19 host genes previously implicated in coronavirus biology. We verify ACE2 and DPP4 as entry receptors for SARS-CoV/SARS-CoV-2 and MERS-CoV respectively. SARS-CoV-2 replication in IOs does not require the endosomal Cathepsin B/L proteases, but specifically depends on the cell surface protease TMPRSS2. Other TMPRSS family members were not essential. The newly emerging coronavirus variant B.1.1.7, as well as SARS-CoV and MERS-CoV similarly depended on TMPRSS2. These findings underscore the relevance of non-transformed human models for coronavirus research, identify TMPRSS2 as an attractive pan-coronavirus therapeutic target, and demonstrate that an organoid knockout biobank is a valuable tool to investigate the biology of current and future emerging coronaviruses.
Identifying cancer pathway dysregulations using differential causal effects
Authors: Jablonski Kim Philipp , Pirkl Martin , Ćevid Domagoj , Bühlmann Peter , Beerenwinkel Niko 
Published: May 2021

AbstractSignaling pathways control cellular behavior. Dysregulated pathways, for example due to mutations that cause genes and proteins to be expressed abnormally, can lead to diseases, such as cancer. We introduce a novel computational approach, called Differential Causal Effects (dce), which compares normal to cancerous cells using the statistical framework of causality. The method allows to detect individual edges in a signaling pathway that are dysregulated in cancer cells, while accounting for confounding. Hence, artificial signals from, for example, batch effects have less influence on the result and dce has a higher chance to detect the biological signals. We show that dce outperforms competing methods on synthetic data sets and on CRISPR knockout screens. In an exploratory analysis on breast cancer data from TCGA, we recover known and discover new genes involved in breast cancer progression.
Cochlear nucleus small cells use olivocochlear collaterals to encode sounds in noise
Authors: Hockley Adam , Wu Calvin , Shore Susan E 
Published: May 2021

ABSTRACTUnderstanding communication signals, especially in noisy environments, is crucial to social interactions. Yet, as we age, acoustic signals can be disrupted by cochlear damage and the subsequent auditory nerve fiber degeneration. The most vulnerable—medium and high-threshold—auditory nerve fibers innervate various cell types in the cochlear nucleus, among which, the small cells are unique in receiving this input exclusively. Furthermore, small cells project to medial olivocochlear (MOC) neurons, which in turn send branched collaterals back into the SCC. Here, we use single-unit recordings to characterise small cell firing characteristics and demonstrate superior intensity coding in this cell class. We show converse effects when activating/blocking the MOC system, demonstrating that small-cell unique coding properties are facilitated by direct cholinergic input from the MOC system. Small cells also maintain tone-level coding in the presence of background noise. Finally, small cells precisely code low-frequency modulation more accurately than other ventral CN (VCN) cell types, demonstrating accurate envelope coding that may be important for vocalisation processing. These results highlight the small cell–olivocochlear circuit as a key player in signal processing in noisy environments, which may be selectively degraded in aging or after noise insult.
Acute SARS-CoV-2 infection is associated with an expansion of bacteria pathogens in the nose including Pseudomonas Aeruginosa
Authors: Rhoades Nicholas S. , Pinski Amanda , Monsibais Alisha N. , Jankeel Allen , Doratt Brianna M. , Cinco Isaac R. , Ibraim Izabela , Messaoudi Ilhem 
Published: May 2021

ABSTRACTMuch of the research conducted on SARS-CoV-2 and COVID-19 has focused on the systemic host response, especially that generated by severely ill patients. Very few studies have investigated the impact of acute SARS-CoV-2 within the nasopharynx, the site of initial infection and viral replication. In this study we profiled changes in the nasal microbial communities as well as in host transcriptional profile during acute SARS-CoV-2 infection using 16S amplicon sequencing and RNA sequencing. These analyses were coupled to viral genome sequencing. Our microbiome analysis revealed that the nasal microbiome of COVID patients was unique and was marked by an expansion of bacterial pathogens. Some of these microbes (i.e. Acinetobacter) were shared with COVID negative health care providers from the same medical center but absent in COVID negative outpatients seeking care at the same institutions suggesting acquisition of nosocomial respiratory pathogens. Specifically, we report a distinct increase in the prevalence and abundance of the pathogen Pseudomonas aeruginosa in COVID patients that correlated with viral RNA load. These data suggest that the inflammatory environment caused by SARS-CoV-2 infection and potentially exposure to the hospital environment leads to an expansion of bacterial pathogens in the nasal cavity that could contribute to increased incidence of secondary bacterial infections. Additionally, we observed a robust host transcriptional response in the nasal epithelia of COVID patients, indicative of an antiviral innate immune repones and neuronal damage. Finally, analysis of viral genomes did not reveal an association between viral loads and viral sequences.
Novel entropy-based metrics for predicting choice behavior based on local response to reward
Authors: Trepka Ethan , Spitmaan Mehran , Bari Bilal A. , Costa Vincent D. , Cohen Jeremiah Y. , Soltani Alireza 
Published: May 2021

AbstractFor decades, behavioral scientists have used the matching law to quantify how animals distribute their choices between multiple options in response to reinforcement they receive. More recently, many reinforcement learning (RL) models have been developed to explain choice by integrating reward feedback over time. Despite reasonable success of RL models in capturing choice on a trial-by-trial basis, these models cannot capture variability in matching. To address this, we developed novel metrics based on information theory and applied them to choice data from dynamic learning tasks in mice and monkeys. We found that a single entropy-based metric can explain 50% and 41% of variance in matching in mice and monkeys, respectively. We then used limitations of existing RL models in capturing entropy-based metrics to construct a more accurate model of choice. Together, our novel entropy-based metrics provide a powerful, model-free tool to predict adaptive choice behavior and reveal underlying neural mechanisms.
Illusory tactile movement crosses arms and legs and is coded in external space
Authors: Martel Marie , Fuchs Xaver , Trojan Jörg , Gockel Valerie , Habets Boukje , Heed Tobias 
Published: May 2021

AbstractHumans often misjudge where on the body a touch occurred. Theoretical accounts have ascribed such misperceptions to local interactions in peripheral and primary somatosensory neurons, positing that spatial-perceptual mechanisms adhere to limb boundaries and skin layout. Yet, perception often reflects integration of sensory signals with prior experience. On their trajectories, objects often touch multiple limbs; therefore, body-environment interactions should manifest in perceptual mechanisms that reflect external space.Here, we demonstrate that humans perceived the cutaneous rabbit illusion – the percept of multiple identical stimuli as hopping across the skin – along the Euclidian trajectory between stimuli on two body parts and regularly mislocalized stimuli from one limb to the other. A Bayesian model based on Euclidian, as opposed to anatomical, distance faithfully reproduced key aspects of participants’ localization behavior.Our results suggest that prior experience of touch in space critically shapes tactile spatial perception and illusions beyond anatomical organization.
RNA silencing by CRISPR in plants does not require Cas13
Authors: Sharma VK , Marla S , Zheng WG , Mishra D , Huang J , Zhang W , Morris GP , Cook DE 
Published: May 2021

AbstractRNA-targeting CRISPR-Cas can provide potential advantages over DNA editing, such as avoiding pleiotropic effects of genome editing, providing precise spatiotemporal regulation and expanded function including anti-viral immunity. Here, we report the use of CRISPR-Cas13 in plants to reduce both viral and endogenous RNA. Unexpectedly, we discovered that crRNA designed to guide Cas13 could, in the absence of the Cas13 protein, cause substantial reduction in RNA levels as well. We demonstrate Cas13-independent guide-induced gene silencing (GIGS) in three plant species, including stable transgenic Arabidopsis. We determined that GIGS utilizes endogenous RNAi machinery despite the fact that crRNA are unlike canonical triggers of RNAi such as miRNA, hairpins or long double-stranded RNA. These results suggest that GIGS offers a novel and flexible approach to RNA reduction with potential benefits over existing technologies for crop improvement. Our results demonstrate that GIGS is active across a range of plant species, evidence similar to recent findings in an insect system, which suggests that GIGS is potentially active across many eukaryotes.
Study on fire resistance of a prefabricated reinforced concrete frame structure
Authors: Li Shufeng , Jiaolei Zhang , Zhao Di , Deng Le 
Published: May 2021

Purpose
This study aims to further study the fire resistance of prefabricated concrete beam-column joints with end-plate connection. This paper aims to analyze the fire resistance of this joint in prefabricated reinforced concrete frame structure (PRCS).

Design/methodology/approach
First, the accuracy of the model is verified by using the test data. Based on this, a refined finite element model of PRCS structure with two stories and two spans is established. The influence of four working conditions with different fire floors (positions) and different axial compression ratios on the deformation, failure and fire resistance of PRCS structure are analyzed.

Findings
The results show that under the four working conditions, the fire resistance of the PRCS structure under Condition 1 and Condition 2 is smaller. It shows that the beam deformation develops slowly in PRCS structure under four kinds of fire positions, and the large displacement emerges 60 min later, which is poles apart from that of prefabricated beam column members. With the increase of the fire time, the material is damaged and deteriorated, which leads to the eccentricity of the axial load, so that the column top appears large lateral displacement. Under the Conditions 1 and 3, the lateral displacement of the column gradually decreases as the axial compression ratio rises.

Originality/value
It is found that there is a distinct lack of researching on the fire resistance of prefabricated joints, and the existed research studies are limited to the fire resistance of members. Thus, it is necessary to strengthen the first floor and side column design of prefabricated frame structure.
The impacts of ambidextrous innovation on organizational obsolescence in turbulent environments
Authors: Chen Shuting , Yu Dengke 
Published: May 2021

PurposeThe authors aim to measure the effects of ambidextrous innovation and its mix strategy on organizational obsolescence with the moderating roles of environmental turbulence.Design/methodology/approachHierarchical regression analysis was used to test the hypotheses on the basis of the survey data of 198 firm employees in China.FindingsBoth exploratory and exploitative innovations significantly restrain organizational obsolescence. The complementary strategy of ambidextrous innovation is negatively correlated to organizational obsolescence, but the impact of balanced strategy is not significant. Environmental turbulence negatively moderates the relationship between exploratory innovation and organizational obsolescence, whereas it cannot moderate the effect of exploitative innovation.Originality/valueThe empirical and conceptual findings have important implications for organizations countering obsolescence through the construction of a mix strategy of ambidextrous innovation. This study enriches and extends obsolescence theory by introducing the joint mechanism of ambidextrous innovation and environmental turbulence.
Option informativeness before earnings announcements and under real activity manipulation
Authors: Gao Xiang , Gu Jiahao , Zhang Yingchao 
Published: May 2021

PurposeThis paper aims to investigate whether single-name options trading prior to earnings announcements is more informative when there exist real activity manipulations.Design/methodology/approachUsing 5,419 earnings announcements during 2004–2018 made by 208 public US companies with relatively high options volumes ranked by the CBOE, the authors uncover two regularities using predictive regressions for stock return.FindingsFirst, the total options volume up to twenty days pre-announcement is significantly higher than that in other periods only for earnings management firms; moreover, after detailing options characteristics, the authors find these intensive pre-announcement trading to be concentrated in transactions of in-the-money call and long-term maturity put options. Second, an increase in the single-name call minus put options volume can positively predict the underlying stock’s next-day excess return much better in real earnings management firms, with a larger magnitude of effect in periods right before regular earnings announcement dates.Originality/valueThis paper makes a marginal and novel contribution by showing that real earnings management can serve as a proxy for the potential profit from informed trading in options as the return predictability of options volume becomes stronger for firms that have the manipulation motive and indeed perform manipulative actions.
Clinical analysis of generalized pustular psoriasis in Chinese patients: A retrospective study of 110 patients
Authors: Zheng Jianfeng , Chen Wenjuan , Gao Yunlu , Chen Fujuan , Yu Ning , Ding Yangfeng , Liu Na 
Published: May 2021

AbstractGeneralized pustular psoriasis is an immune‐mediated dermatologic condition characterized by widespread, sterile, subcorneal pustules. However, limited information exists regarding the clinical course of generalized pustular psoriasis. This study aimed to examine the precipitating factors, clinical manifestations, laboratory data, relapse patterns, and prognosis of generalized pustular psoriasis at our hospital and to improve the diagnosis and treatment. A retrospective analysis was conducted for generalized pustular psoriasis in our department from 2014 to 2019. In total, 110 patients were included in our study (mean age 46.5 years). The female:male ratio was 1:2.7. Ninety‐four (85.5%) had a psoriasis vulgaris history, 12 (10.9%) had a psoriatic arthritis history, five (4.5%) had an erythrodermic psoriasis history, and 16 (14.5%) had a family history of psoriasis. Eleven (10.0%) cases were triggered by infections and 17 (15.5%) were caused by the sudden discontinuation of systemic drugs. During hospitalization, the proportion of patients with hyperlipidemia was higher after acitretin treatment than before acitretin treatment (P < 0.05). The proportion of patients with abnormal liver function was higher after methotrexate treatment than before methotrexate treatment (P > 0.05). The onset age of generalized pustular psoriasis was younger in patients without prior psoriasis (P < 0.05). The mean time to pustular clearance was shorter in patients with prior psoriasis than in those without prior psoriasis (P > 0.05). Moreover, among patients with fever, skin lesion clearance rates were highest in the biological agent group (81.8%). However, among patients without fever, skin lesion clearance rates were highest in the acitretin group (86.7%). No patients presented serious complications or died. Our study presents the detailed clinical course of generalized pustular psoriasis in Chinese patients. These results will help to better understand and treat generalized pustular psoriasis.
Wider crown shyness between broad‐leaved tree species than between coniferous tree species in a mixed forest of Castanopsis cuspidata and Chamaecyparis obtusa
Authors: Onoda Yusuke , Bando Reo 
Published: May 2021

AbstractPersistent openings (gaps) between adjacent crowns at similar heights can be found in tall forests. Such openings are called “crown shyness” and are formed through the collision of tree crowns during high winds. While crown shyness has been studied in plantations, much less studied in natural forests despite its importance for light acquisition, competition, and coexistence. In this study, we focused on a mixed forest in Japan, and examined a hypothesis that broad‐leaved tree species, which often have top‐wide crowns, have wider crown shyness than coniferous tree species, which often have narrow cone‐shape crowns, because top‐wide crowns may be more exposed to wind and more likely to collide with their neighbors. Crown shyness, which was measured by drone imagery, was clearly found between individuals of the broad‐leaved tree species Castanopsis cuspidata but not between the coniferous tree species Chamaecyparis obtusa. This interspecific difference may be associated with differences in crown shape; Castanopsis had wider (1.57‐fold) and shallower (0.64‐fold) crowns than Chamaecyparis. Within Castanopsis, the size of crown shyness tended to negatively correlated with stem diameter and positively correlated with stem slenderness. Our study showed that the difference in crown shape among species is one of the key factors in determining the size of crown shyness. Top‐wide crowns of broad‐leaved trees compared to conifers may have a competitive advantage in light interception, but it may come at the cost of crown collisions with adjacent crowns and resulting in persistent openings at the canopy layer.
White Suits and Kangaroo Kills: Making Men's Careers in American Nursing
Authors: Elder Rachel 
Published: May 2021

AbstractThis article explores nursing as an emerging career path for men in interwar America. As women reached historic concentrations within the profession, it examines how early gradutes of the Pennsylvania Hospital School of Nursing for Men created a distinct form of gendered professionalism that allowed them to enter an otherwise female‐dominated field. Drawing on school records and oral histories, it argues that men's training simultaneously integrated the feminised aspects of caring labour while upholding strict codes of masculinity that also excluded gay men and men of colour. In contrast to the few existing studies of men in traditionally female fields throughout the twentieth century, this case thus more closely resembles histories of women in male‐dominated professions, in which participants calibrated their presentations of gender to appease both gender and professional norms.
Using two‐holed needles for both arterial and venous accesses to the arteriovenous fistula to improve flow during hemodialysis
Authors: Yilmaz Ustun , Unal Aysun , Gul Semih , Demirtas Gulay , Inci Ayca , Sahinturk Yasin 
Published: May 2021

AbstractThis prospective study compared methods using both arterial and venous needles with back eyes with those using only arterial needle with back eye for arteriovenous fistula cannulation. Sixty‐one patients receiving hemodialysis (HD) via an arteriovenous fistula were evaluated. All patients underwent arteriovenous fistula puncture using only arterial needle with back eye in first 3 months and both arterial and venous needles with back eyes in following 3 months. Arterial and venous pressures, blood flow velocities, total blood volume cleared, and Kt/V values were compared. Mean blood flow velocity, arterial pressure, Kt/V, and cleared total blood volume values were higher and venous pressure was lower in patients who underwent cannulation using both needles with back eyes than in those with only the arterial needle with back eye. For arteriovenous fistula cannulation, using both arterial and venous needles with back eyes provides adequate HD more successfully.
Combining comparative genomic analysis with machine learning reveals some promising diagnostic markers to identify five common pathogenic non‐tuberculous mycobacteria
Authors: Jia Xinmiao , Yang Linfang , Li Cuidan , Xu Yingchun , Yang Qiwen , Chen Fei 
Published: May 2021

SummaryNon‐tuberculous mycobacteria (NTM) can cause various respiratory diseases and even death in severe cases, and its incidence has increased rapidly worldwide. To date, it’s difficult to use routine diagnostic methods and strain identification to precisely diagnose various types of NTM infections. We combined systematic comparative genomics with machine learning to select new diagnostic markers for precisely identifying five common pathogenic NTMs (Mycobacterium kansasii, Mycobacterium avium, Mycobacterium intracellular, Mycobacterium chelonae, Mycobacterium abscessus). A panel including six genes and two SNPs (nikA, benM, codA, pfkA2, mpr, yjcH, rrl C2638T, rrl A1173G) was selected to simultaneously identify the five NTMs with high accuracy (> 90%). Notably, the panel only containing the six genes also showed a good classification effect (accuracy > 90%). Additionally, the two panels could precisely differentiate the five NTMs from M. tuberculosis (accuracy > 99%). We also revealed some new marker genes/SNPs/combinations to accurately discriminate any one of the five NTMs separately, which provided the possibility to diagnose one certain NTM infection precisely. Our research not only reveals novel promising diagnostic markers to promote the development of precision diagnosis in NTM infectious, but also provides an insight into precisely identifying various genetically close pathogens through comparative genomics and machine learning.
Novel virocell metabolic potential revealed in agricultural soils by virus‐enriched soil metagenome analysis
Authors: Braga Lucas P. P. , Coutinho Felipe H. , Amgarten Deyvid E. , Kot Witold , Hansen Lars , Setubal João C. , Philippot Laurent 
Published: May 2021

SummaryViruses are now recognized as important players in microbial dynamics and biogeochemical cycles in the oceans. Yet, compared with aquatic ecosystems, virus discovery in terrestrial ecosystems has been challenging partly due to the inherent complexity of soils. To expand our understanding of soil viruses and their putative contributions to soil microbial processes, we analysed metagenomes of community‐level virus‐enriched suspensions by tangential flow filtration obtained from two French agricultural soils. We found viral sequences representing a total of 239 viral operational taxonomic units that corresponded to 29.5% of the mapping reads in the metagenomic datasets. The analysis of their genomic sequences revealed novel virocell metabolic potential with implications to virus–host interactions, carbon cycling, plant‐beneficial functions in the rhizosphere, horizontal gene transfer and other relevant microbial strategies applied to survive in soils.