bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput CRISPRi and CRISPRa technologies in 3D genome regulation for neuropsychiatric diseases
Authors: Jones Ian R , Ren Xingjie , Shen Yin 
Published: August 2022

Abstract
Advances in genomics have led to the identification of many risk loci with hundreds of genes and thousands of DNA variants associated with neuropsychiatric disorders. A significant barrier to understanding the genetic underpinnings of complex diseases is the lack of functional characterization of risk genes and variants in biological systems relevant to human health and connecting disease-associated variants to pathological phenotypes. Characterizing gene and DNA variant functions requires genetic perturbations followed by molecular and cellular assays of neurobiological phenotypes. However, generating null or mutant alleles is low throughput, making it impossible to characterize disease-associated variants in large quantities efficiently. CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) screens can be leveraged to dissect the biological consequences of the tested genes and variants in their native context. Nevertheless, testing non-coding variants associated with complex diseases remains non-trivial. In this review, we first discuss the current challenges of interpreting the function of the non-coding genome and approaches to prioritizing disease-associated variants in the context of the 3D epigenome. Second, we provide a brief overview of high-throughput CRISPRi and CRISPRa screening strategies applicable for characterizing non-coding sequences in appropriate biological systems. Lastly, we discuss the promising prospects of using CRISPR-based technologies to dissect DNA sequences associated with neuropsychiatric diseases.
IBD Flare in the COVID-19 Pandemic: Therapy Discontinuation Is to Blame
Authors: Bezzio Cristina , Fiorino Gionata , Ribaldone Davide G , Armuzzi Alessandro , Saibeni Simone ,   IG-IBD COVID-19 Study Group, Vernero Marta , Furfaro Federica , Pugliese Daniela , Manes Gianpiero , Pastorelli Luca , Gerardi Viviana , Viganò Chiara , Variola Angela , Caprioli Fabio , Zingone Fabiana , Scucchi Ludovica , Ardizzone Sandro , Baroni Stefania , Ricci Chiara , Onali Sara , Balestrieri Paola , Roselli Jenny , Bodini Giorgia , Daperno Marco , Lenti Marco , Baldoni Monia , Carparelli Sonia , Casini Valentina , Felice Carla , Cortelezzi Claudio , Amato Arnaldo , Mazzuoli Silvia , Coppini Francesca , Sartini Alessandro , Soriano Alessandra , Viscido Angelo , Buda Andrea , Grossi Laurino , Allocca Mariangela , Privitera Giuseppe , Armandi Angelo 
Published: August 2022

Lay Summary
This prospective case-control study investigated the impact of severe acute respiratory syndrome coronavirus 2 infection on inflammatory bowel disease course and looked for risk factors associated with flares. In the severe acute respiratory syndrome coronavirus 2 pandemic era, inflammatory bowel disease course is not influenced by infection, while therapy discontinuation is a risk factor for disease flare.
Patient-Reported Outcomes Correlate With Microbial Community Composition Independent of Mucosal Inflammation in Pediatric Inflammatory Bowel Disease
Authors: Hellmann Jennifer , Ta Allison , Ollberding Nicholas J , Bezold Ramona , Lake Kathleen , Jackson Kimberly , Dirksing Kelsie , Bonkowski Erin , Haslam David B , Denson Lee A 
Published: August 2022

Abstract

Background
Inflammatory bowel diseases (IBDs) involve an aberrant host response to intestinal microbiota causing mucosal inflammation and gastrointestinal symptoms. Patient-reported outcomes (PROs) are increasingly important in clinical care and research. Our aim was to examine associations between PROs and fecal microbiota in patients 0 to 22 years of age with IBD.

Methods
A longitudinal, prospective, single-center study tested for associations between microbial community composition via shotgun metagenomics and PROs including stool frequency and rectal bleeding in ulcerative colitis (UC) and abdominal pain and stool frequency in Crohn’s disease (CD). Mucosal inflammation was assessed with fecal calprotectin. A negative binomial mixed-effects model including clinical characteristics and fecal calprotectin tested for differentially abundant species and metabolic pathways by PROs.

Results
In 70 CD patients with 244 stool samples, abdominal pain correlated with increased relative abundance of Haemophilus and reduced Clostridium spp. There were no differences relative to calprotectin level. In 23 UC patients with 76 samples, both rectal bleeding and increased stool frequency correlated with increased Klebsiella and reduced Bacteroides spp. Conversely, UC patients with lower calprotectin had reduced Klebsiella. Both UC and CD patients with active symptoms exhibited less longitudinal microbial community stability. No differences in metabolic pathways were observed in CD. Increased sulfoglycolysis and ornithine biosynthesis correlated with symptomatic UC.

Conclusions
Microbial community composition correlated with PROs in both CD and UC. Metabolic pathways differed relative to PROs in UC, but not CD. Data suggest that microbiota may contribute to patient symptoms in IBD, in addition to effects of mucosal inflammation.
Hidden dissemination of carbapenem-susceptible OXA-48-producing Proteus mirabilis
Authors: Pedraza Rosa , Kieffer Nicolas , Guzmán-Puche Julia , Artacho María José , Pitart Cristina , Hernández-García Marta , Vila Jordi , Cantón Rafael , Martinez-Martinez Luis 
Published: August 2022

Abstract

Objectives
To detect a potential hidden dissemination of the blaOXA-48 gene among Proteus mirabilis isolates obtained from a single centre.

Methods
P. mirabilis from diverse clinical samples presenting an ESBL phenotype or obtained from blood cultured from 2017 to 2019 were evaluated. Bacterial identification was performed using MALDI-TOF MS. MICs were determined using International Organization for Standardization (ISO) standard microdilution and interpreted following EUCAST guidelines. WGS was performed using both short- and long-read technologies and assemblies were done using Unicycler. Resistomes were assessed using the ResFinder database. SNPs were detected using the PATRIC bioinformatics platform. Cloning experiments were performed using the pCRII-TOPO cloning kit.

Results
Thirty-one out of 108 (28.7%) isolates were positive for blaOXA-48 and blaCTX-M-15. Twenty-nine out of 31 of the isolates were susceptible to temocillin, piperacillin/tazobactam, ertapenem and meropenem, whereas only 2/31 showed a resistance phenotype against these antibiotics. Both blaOXA-48 and blaCTX-M-15 genes were detected within the same chromosomally integrated new transposon in all isolates. The resistant isolates displayed a single mutation located in the putative promoter upstream of blaOXA-48. Cloning experiments confirmed that the mutation was responsible for the resistance phenotype.

Conclusions
The presence of a chromosomal copy of blaOXA-48 did not confer resistance to carbapenems, but a single mutation in the promoter could lead to an increase in resistance. This study shows a hidden circulation of OXA-48-positive, but carbapenem- and piperacillin/tazobactam-susceptible, P. mirabilis isolates that can become resistant to β-lactams after a single mutation.
Activity of ertapenem/zidebactam (WCK 6777) against problem Enterobacterales
Authors: Mushtaq Shazad , Garello Paolo , Vickers Anna , Woodford Neil , Livermore David M 
Published: August 2022

Abstract

Background
Secondary healthcare will remain pressured for some years, both because SARS-CoV-2 will circulate as a nosocomial pathogen, and owing to backlogs of patients awaiting delayed elective procedures. These stresses will drive the use of Outpatient Parenteral Antibiotic Therapy (OPAT), which will need to cover increasingly resistant Gram-negative opportunists. We evaluated the activity of ertapenem/zidebactam, proposed for 2 + 2 g q24h administration.

Materials and methods
MICs were determined, by BSAC agar dilution, for 1632 Enterobacterales submitted to the UK national reference laboratory for investigation of antimicrobial resistance.

Results
Over 90% of Escherichia coli with AmpC, ESBLs, KPC, metallo- or OXA-48 carbapenemases were inhibited by ertapenem/zidebactam 1:1 at ertapenem’s current 0.5 mg/L breakpoint. For other major Enterobacterales, the proportions inhibited by ertapenem/zidebactam 1:1 at 0.5 mg/L were mostly 65% to 90% but were lower for Klebsiella pneumoniae/oxytoca with metallo- or OXA-48 β-lactamases. However, animal studies support an 8 mg/L breakpoint for ertapenem/zidebactam, based on a shortened T&gt;MIC being needed compared with ertapenem alone. On this basis ertapenem/zidebactam would count as active against 90%–100% of isolates in all groups except K. pneumoniae/oxytoca with MBLs (±OXA-48), where MICs and percent susceptibility vary substantially even with inocula within the BSAC acceptable range.

Conclusions
Ertapenem/zidebactam has a proposed once-daily regimen well suited to OPAT. Even on highly conservative breakpoint projections, it has potential against MDR E. coli, including metallo-carbapenemase producers. If trial data sustain the 8 mg/L breakpoint indicated by animal experiments, its potential will extend widely across infections due to ESBL-, AmpC- and carbapenemase-producing Enterobacterales.
N4-acetylcytidine regulates the replication and pathogenicity of enterovirus 71
Authors: Hao Haojie , Liu Weichi , Miao Yuanjiu , Ma Li , Yu Baocheng , Liu Lishi , Yang Chunjie , Zhang Kui , Chen Zhen , Yang Jingwen , Zheng Zhenhua , Zhang Bo , Deng Fei , Gong Peng , Yuan Jianhui , Hu Zhangli , Guan Wuxiang 
Published: August 2022

Abstract
Chemical modifications are important for RNA function and metabolism. N4-acetylcytidine (ac4C) is critical for the translation and stability of mRNA. Although ac4C is found in RNA viruses, the detailed mechanisms through which ac4C affects viral replication are unclear. Here, we reported that the 5′ untranslated region of the enterovirus 71 (EV71) genome was ac4C modified by the host acetyltransferase NAT10. Inhibition of NAT10 and mutation of the ac4C sites within the internal ribosomal entry site (IRES) suppressed EV71 replication. ac4C enhanced viral RNA translation via selective recruitment of PCBP2 to the IRES and boosted RNA stability. Additionally, ac4C increased the binding of RNA-dependent RNA polymerase (3D) to viral RNA. Notably, ac4C-deficient mutant EV71 showed reduced pathogenicity in vivo. Our findings highlighted the essential role of ac4C in EV71 infection and provided insights into potential antiviral treatments.
Magnetically encoded 3D mesostructure with high-order shape morphing and high-frequency actuation
Authors: Li Rui , Zhang Cong , Li Jiawen , Zhang Yachao , Liu Shunli , Hu Yanlei , Jiang Shaojun , Chen Chao , Xin Chen , Tao Yuan , Dong Bin , Wu Dong , Chu Jiaru 
Published: August 2022

Abstract
Inspired by origami/kirigami, three-dimensional (3D) mesostructures assembled via a mechanics-guided approach, with reversible and maneuverable shape-morphing capabilities, have attracted great interest with regard to a broad range of applications. Despite intensive studies, the development of morphable 3D mesostructures with high-order (multi-degree-of-freedom) deformation and untethered high-frequency actuation remains challenging. This work introduces a scheme for a magnetically encoded transferable 3D mesostructure, with polyethylene terephthalate (PET) film as the skeleton and discrete magnetic domains as actuation units, to address this challenge. The high-order deformation, including hierarchical, multidirectional and blending shape morphing, is realized by encoding 3D discrete magnetization profiles on the architecture through ultraviolet curing. Reconfigurable 3D mesostructures with a modest structural modulus (∼3 GPa) enable both high-frequency (∼55 Hz) and large-deformation (∼66.8%) actuation under an alternating magnetic field. Additionally, combined with the shape-retention and adhesion property of PET, these 3D mesostructures can be readily transferred and attached to many solid substrates. On this basis, diverse functional devices, including a switchable colour letter display, liquid mixer, sequential flashlight and biomimetic sliding robot, are demonstrated to offer new perspectives for robotics and microelectronics.
From Start to Finish: Examining Factors Associated With Higher Likelihood of Publication Among Abstracts Presented at an International Infectious Diseases Scientific Meeting
Authors: Johnson Asia J , Bland Christopher M , Teng Chengwen , Zheng Lily , Hungerpiller J Colin , Easterling Morgan , Arnold Sarah , Dean Madeline , Royals Carrington , Bookstaver P Brandon 
Published: August 2022

Abstract

Background
The landscape of infectious diseases research by interprofessional teams continues to change in both scope and engagement. Limited information exists regarding publication metrics and factors associated with publication of abstracts presented at professional infectious diseases meetings.

Methods
This was a retrospective, observational study evaluating abstracts presented at IDWeek in 2017 and 2018. The primary endpoint was the proportion of abstracts that were subsequently published in peer-reviewed journals. Factors associated with publication were evaluated, and a description of publication metrics was reported.

Results
Of the 887 abstracts analyzed from the IDWeek meetings, 236 (26.6%) were published. Significantly more abstracts were published if they were presented as a platform presentation versus poster presentation (35% vs 21%, P &lt; .001). Inclusion of a PhD author significantly increased the likelihood of publication (P = .0014). Prospective studies, greater number of authors, and greater number of study subjects were more common among published abstracts. Median time to publication was 10.9 months, and the majority were published in infectious diseases journals, with an overall average impact factor of 7.7 across all journals.

Conclusions
Abstracts from IDWeek presented as oral platforms and those including a PhD author were more likely to be published. Large, diverse authorship teams were common among published abstracts. The high quality of resulting manuscripts is evident by the destination journals and their respective impact factors. These data may be used to inform and motivate clinicians and trainees engaging in infectious diseases–related research.
GhTCE1–GhTCEE1 dimers regulate transcriptional reprogramming during wound-induced callus formation in cotton
Authors: Deng Jinwu , Sun Weinan , Zhang Boyang , Sun Simin , Xia Linjie , Miao Yuhuan , He Liangrong , Lindsey Keith , Yang Xiyan , Zhang Xianlong 
Published: August 2022

Abstract
Wounded plant cells can form callus to seal the wound site. Alternatively, wounding can cause adventitious organogenesis or somatic embryogenesis. These distinct developmental pathways require specific cell fate decisions. Here, we identify GhTCE1, a basic helix–loop–helix family transcription factor, and its interacting partners as a central regulatory module of early cell fate transition during in vitro dedifferentiation of cotton (Gossypium hirsutum). RNAi- or CRISPR/Cas9-mediated loss of GhTCE1 function resulted in excessive accumulation of reactive oxygen species (ROS), arrested callus cell elongation, and increased adventitious organogenesis. In contrast, GhTCE1-overexpressing tissues underwent callus cell growth, but organogenesis was repressed. Transcriptome analysis revealed that several pathways depend on proper regulation of GhTCE1 expression, including lipid transfer pathway components, ROS homeostasis, and cell expansion. GhTCE1 bound to the promoters of the target genes GhLTP2 and GhLTP3, activating their expression synergistically, and the heterodimer TCE1-TCEE1 enhances this activity. GhLTP2- and GhLTP3-deficient tissues accumulated ROS and had arrested callus cell elongation, which was restored by ROS scavengers. These results reveal a unique regulatory network involving ROS and lipid transfer proteins, which act as potential ROS scavengers. This network acts as a switch between unorganized callus growth and organized development during in vitro dedifferentiation of cotton cells.
AIG2A and AIG2B limit the activation of salicylic acid-regulated defenses by tryptophan-derived secondary metabolism in Arabidopsis
Authors: Wang Zhixue , Yang Leiyun , Jander Georg , Bhawal Ruchika , Zhang Sheng , Liu Zhenhua , Oakley Aaron , Hua Jian 
Published: August 2022

Abstract
Chemical defense systems involving tryptophan-derived secondary metabolites (TDSMs) and salicylic acid (SA) are induced by general nonself signals and pathogen signals, respectively, in Arabidopsis thaliana. Whether and how these chemical defense systems are connected and balanced is largely unknown. In this study, we identified the AVRRPT2-INDUCED GENE2A (AIG2A) and AIG2B genes as gatekeepers that prevent activation of SA defense systems by TDSMs. These genes also were identified as important contributors to natural variation in disease resistance among A. thaliana natural accessions. The loss of AIG2A and AIG2B function leads to upregulation of both SA and TDSM defense systems. Suppressor screens and genetic analysis revealed that a functional TDSM system is required for the upregulation of the SA pathway in the absence of AIG2A and AIG2B, but not vice versa. Furthermore, the AIG2A and AIG2B genes are co-induced with TDSM biosynthesis genes by general pathogen elicitors and nonself signals, thereby functioning as a feedback control of the TDSM defense system, as well as limiting activation of the SA defense system by TDSMs. Thus, this study uncovers an AIG2A- and AIG2B-mediated mechanism that fine-tunes and balances SA and TDSM chemical defense systems in response to nonpathogenic and pathogenic microbes.
Cell- and noncell-autonomous AUXIN RESPONSE FACTOR3 controls meristem proliferation and phyllotactic patterns
Authors: Zhang Ke , Zhang Hao , Pan Yanyun , Niu Yanxiao , Guo Lin , Ma Yuru , Tian Shijun , Wei Jiarong , Wang Cong , Yang Xiubo , Fu Yunze , Qu Ping , Liu Liantao , Zhang Yongjiang , Sun Hongchun , Bai Zhiying , Dong Jingao , Li Cundong , Liu Xigang 
Published: August 2022

Abstract
In cell–cell communication, noncell-autonomous transcription factors play vital roles in controlling plant stem cell fate. We previously reported that AUXIN RESPONSE FACTOR3 (ARF3), a member of the ARF family with critical roles in floral meristem maintenance and determinacy, has a distinct accumulation pattern that differs from the expression domain of its encoding gene in the shoot apical meristem (SAM). However, the biological meaning of this difference is obscure. Here, we demonstrate that ARF3 expression in Arabidopsis (Arabidopsis thaliana) is mainly activated at the periphery of the SAM by auxin where ARF3 cell autonomously regulates the expression of meristem–organ boundary-specific genes, such as CUP-SHAPED COTYLEDON1-3 (CUC1-3), BLADE ON PETIOLE1-2 (BOP1-2), and TARGETS UNDER ETTIN CONTROL3 (TEC3) to regulate the arrangement of organs in regular pattern, a phenomenon referred to as phyllotaxis. We also show that ARF3 is translocated into the organizing center where it represses cytokinin activity and WUSCHEL expression to regulate meristem activity noncell-autonomously. Therefore, ARF3 acts as a molecular link that mediates the interaction of auxin and cytokinin signaling in the SAM while coordinating the balance between meristem maintenance and organogenesis. Our findings reveal an ARF3-mediated coordination mechanism through cell–cell communication in dynamic SAM maintenance.
Asset Prices and Unemployment Fluctuations: A Resolution of the Unemployment Volatility Puzzle
Authors: Kehoe Patrick J , Lopez Pierlauro , Midrigan Virgiliu , Pastorino Elena 
Published: August 2022

Abstract
Recent work has demonstrated that existing solutions of the unemployment volatility puzzle are at odds with the procylicality of the opportunity cost of employment, the cyclicality of wages, and the volatility of risk-free rates. We propose a model of business cycles that is immune to these critiques by incorporating two key features. First, we allow for preferences that generate time-varying risk over the business cycle to account for observed fluctuations in asset prices. Second, we introduce human capital acquisition, as is consistent with the evidence on how wages grow with experience in the labor market. Our model reproduces the observed fluctuations in unemployment because hiring a worker is a risky investment with long-duration returns. As in the data, the price of risk in our model sharply increases in recessions. The benefit from hiring new workers therefore greatly declines, leading to a large decrease in job vacancies and an increase in unemployment of the same magnitude as in the data. We show that our results extend to versions of the model that include physical capital, a life cycle for workers, and alternative preference structures common in the asset-pricing literature.
AOSD endotypes based on immune cell profiles: patient stratification with hierarchical clustering analysis
Authors: Guo Ruru , Liu Xuesong , Li Yixuan , Meng Xinyu , Li Rui , Chen Xiaoxiang , Lu Liangjing 
Published: August 2022

AbstractObjectivesThis study aimed to analyse the immune cell profiles of adult-onset Still’s disease (AOSD) and to stratify disease-associated endotypes.MethodsWe included 95 cases of treatment-naïve patients with AOSD and 66 cases of healthy controls. Patients with AOSD were classified via an unbiased hierarchical cluster analysis based on circulating immune cells. Their clinical and laboratory characteristics, treatment management, systemic scores and outcomes were then analysed.ResultsThe proportions of neutrophils and CD8+ T cells were significantly higher while monocytes and natural killer and CD4+ T cells were decreased in patients with AOSD (all P &lt; 0.005). Unbiased hierarchical cluster analysis classified 95 AOSD into three endotype-based groups: group 1 had the highest percentage of neutrophils (neu-dominant group), group 2 had the highest percentage of monocytes (mono-dominant group) and group 3 had the highest percentage of CD8+ T cells (CD8-dominant group). Patients in group 3 had the highest systemic score at diagnosis and were more likely to have pulmonary infiltrates, pericarditis, splenomegaly and poorer treatment responses. A correlation study revealed that the CD4 to CD8 ratio was negatively correlated with the systemic score and positively correlated with treatment response in patients with AOSD (P = 0.001 and P = 0.0091). During the 24.6 (15.2) months of follow-up, the highest total number of disease flares occurred in group 3 (P &lt; 0.0001).ConclusionHierarchical cluster analysis of peripheral immune cells classified AOSD into three disease-related endotypes. Group 3 showed higher systemic score and poorer treatment responses.