bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Pathogenicity of a New Entomopathogenic Fungus, Mucor hiemalis (Mucorales: Mucorales), on the Root Maggot, Bradysia odoriphaga (Diptera: Sciaridae)
Authors: Zhu Guodong , Ding Wenjuan , Xue Ming , Zhao Yongfei , Li Mingzhu , Li Zizheng
Published: January 2022

Bradysia odoriphaga Yang and Zhang (Diptera: Sciaridae), the Chinese chive root maggot, is a destructive pest of Allium vegetables and flowers that causes severe losses in northern China. Novel biological control technologies are needed for controlling this pest. We identified a new entomopathogenic fungus isolated from infected B. odoriphaga larvae and evaluated the susceptibility of the biological stages of B. odoriphaga and the effects of temperature on fungus growth and pathogenicity. Based on morphological characteristics and molecular phylogeny, the fungus was identified as Mucor hiemalis BO-1 (Mucorales: Mucorales). This fungus had the strongest virulence to B. odoriphaga larvae followed by eggs and pupae, while B. odoriphaga adults were not susceptible. A temperature range of 18–28°C was optimum for the growth and sporulation of M. hiemalis BO-1 and virulence to B. odoriphaga larvae. At 3 and 5 d after inoculation with 105 spores/ml at 23°C, the survival rates were 24.8% and 4.8% (2nd instar larvae), respectively, and 49.6% and 12.8% (4th instar larvae), respectively. The potted plant trials confirmed that M. hiemalis BO-1 exerted excellent control efficiency against B. odoriphaga larvae, and the control exceeded 80% within 5 d when the spore concentration applied exceeded 107 spores/ml. In conclusion, these findings supported the hypotheses that this fungus could serve as an effective control agent against B. odoriphaga larvae and is worth being further tested to determine its full potential as a biocontrol agent.
A preliminary study on the detection of lymph node metastasis in cervical cancer using a quantitative RT-PCR assay
Authors: Togami Shinichi , Fukuda Mika , Yanazume Shintaro , Kamio Masaki , Kobayashi Hiroaki
Published: January 2022

Objective

This preliminary study aimed to assess the detection accuracy of sentinel lymph node metastasis in cervical cancer using quantitative reverse transcriptase-polymerase chain reaction.

Methods

We collected cervical cancer tissues and 70 pelvic lymph node samples from patients with cervical cancer. The quantitative reverse transcriptase-polymerase chain reaction assay was performed to investigate the expression of cytokeratin 19 mRNA in cervical cancer tissues and determine the cutoff value of cytokeratin 19 mRNA between the non-metastatic and metastatic lymph nodes.

Results

The expression of cytokeratin 19 mRNA in cancer tissues was detected in all (71/71) the tumours, with a median copy number of 7.56 × 105/μl of RNA by quantitative reverse transcriptase-polymerase chain reaction. Sixteen lymph nodes were diagnosed as positive by pathological examination. The median copy numbers of cytokeratin 19 mRNA for positive and negative lymph nodes were 43.3 × 104/μl and 121.1/μl, respectively. The expression of cytokeratin 19 mRNA in pathologically positive lymph nodes was higher than that in the negative lymph nodes (P < 0.0001) by quantitative reverse transcriptase-polymerase chain reaction analysis. Using a receiver operating characteristic plot, the maximum sensitivity (100%) and specificity (94.4%) were obtained when the cutoff value was set at 1169 copies/μl.

Conclusions

After setting the cutoff value at 1169 copies/μl, a quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA showed high accuracy in detecting lymph node metastasis in cervical cancer. We believe that the quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA may be acceptable for lymph node metastasis detection in patients with cervical cancer.
Racialized Burdens: Applying Racialized Organization Theory to the Administrative State
Authors: Ray Victor , Herd Pamela , Moynihan Donald
Published: January 2022

This article develops the concept of racialized burdens as a means of examining the role of race in administrative practice. Racialized burdens are the experience of learning, compliance and psychological costs that serve as inequality reproducing mechanisms. To develop this concept, we examine administrative burdens in the US state from the theoretical perspective of racialized organizations. Using examples from attempts to access citizenship rights—via immigration, voting and the social safety net—we illustrate some key points. First, racialized burdens combine control of access to resources and ideas about racial groups in ways that typically disadvantage racially marginalized groups. Second, while still promising fair and equal treatment, racially disproportionate burdens can be laundered through facially neutral rules and via claims that burdens are necessary for unrelated reasons. Third, racialized burdens emerge when more explicit forms of racial bias in policies or administrative practices become illegal, politically untenable or culturally unacceptable. Racialized burdens neatly carry out the “how” in the production of racial inequality while concealing, or providing an alibi for, the “why.”
Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study
Authors: Sánchez-Rico Marina , de la Muela Pedro , Herrera-Morueco Juan J , Geoffroy Pierre A , Limosin Frédéric , Hoertel Nicolas ,   AP-HP/Université de Paris/INSERM COVID-19 Research Collaboration/AP-HP COVID CDR Initiative/Entrepôt de Données de Santé AP-HP Consortium
Published: January 2022

In this multicenter retrospective observational study involving 58 562 adult patients hospitalized for COVID-19, melatonin use (N = 272) at a mean daily dose of 2.6 mg was not associated with reduced mortality.
Weather variables as important clinical predictors of bacterial diarrhoea among international travellers
Authors: Pender Melissa A , Smith Timothy , Brintz Ben J , Pandey Prativa , Shrestha Sanjaya K , Anuras Sinn , Demons Samandra , Sornsakrin Siriporn , Bodhidatta Ladaporn , Platts-Mills James A , Leung Daniel T
Published: January 2022

Background

Clinicians and travellers often have limited tools to differentiate bacterial from non-bacterial causes of travellers’ diarrhoea (TD). Development of a clinical prediction rule assessing the aetiology of TD may help identify episodes of bacterial diarrhoea and limit inappropriate antibiotic use. We aimed to identify predictors of bacterial diarrhoea among clinical, demographic and weather variables, as well as to develop and cross-validate a parsimonious predictive model.

Methods

We collected de-identified clinical data from 457 international travellers with acute diarrhoea presenting to two healthcare centres in Nepal and Thailand. We used conventional microbiologic and multiplex molecular methods to identify diarrheal aetiology from stool samples. We used random forest and logistic regression to determine predictors of bacterial diarrhoea.

Results

We identified 195 cases of bacterial aetiology, 63 viral, 125 mixed pathogens, 6 protozoal/parasite and 68 cases without a detected pathogen. Random forest regression indicated that the strongest predictors of bacterial over viral or non-detected aetiologies were average location-specific environmental temperature and red blood cell on stool microscopy. In 5-fold cross-validation, the parsimonious model with the highest discriminative performance had an area under the receiver operator curve of 0.73 using 3 variables with calibration intercept −0.01 (standard deviation, SD 0.31) and slope 0.95 (SD 0.36).

Conclusions

We identified environmental temperature, a location-specific parameter, as an important predictor of bacterial TD, among traditional patient-specific parameters predictive of aetiology. Future work includes further validation and the development of a clinical decision-support tool to inform appropriate use of antibiotics in TD.
Comparative evaluation of Sensititre YeastOne and VITEK 2 against the Clinical and Laboratory Standards Institute M27-E4 reference broth microdilution method for the antifungal susceptibility testing of Cryptococcus neoformans and Cryptococcus gattii
Authors: Zhang Min , Zhou Ziyi , Wang Dongjiang , Zhou Aiping , Song Guobin , Chen Xingchun , Guo Jian , Wu Wenjuan
Published: January 2022

The present study collected 280 isolates of Cryptococcus neoformans and 22 isolates of Cryptococcus gattii and evaluated the consistencies between Sensititre YeastOne (SYO), VITEK 2, and the reference broth microdilution (BMD) method for the antifungal susceptibility testing of fluconazole, voriconazole, and flucytosine. For amphotericin B, SYO was replaced with the BIO KONT amphotericin B microbroth dilution kit. The essential agreements (EAs) by SYO and VITEK 2 for C. neoformans var. grubii and C. neoformans var. neoformans were 98.15–99.63% and 88.89–100%, respectively, with fluconazole, voriconazole, and flucytosine. The EA for C. gattii VG Ⅰ against fluconazole was 29.41% by VITEK 2, while the other EAs for C. gattii strains were 100% by SYO and VITEK 2. The categorical agreements (CAs) by SYO and VITEK 2 for C. neoformans and C. gattii were 94.12–100%, while VITEK 2 failed to distinguish 5/6 fluconazole-resistant non-wild-type C. neoformans var. grubii isolates; this finding confirmed the limitation of testing fluconazole against C. neoformans as documented in the manufacturer's package insert. The EAs for amphotericin B were 97.42–100% for C. neoformans and C. gattii, but the CAs were 17.65–60% by BIO KONT and VITEK 2. Thus, SYO can be used for susceptibility testing of C. neoformans and C. gattii against fluconazole, voriconazole, and flucytosine, and VITEK 2 can be used for susceptibility testing of C. neoformans against voriconazole and flucytosine. Further studies using amphotericin B-resistant isolates are required to assess the agreement between VITEK 2, BIO KONT, and BMD.

Lay Summary

Sensititre YeastOne showed a good agreement with the CLSI broth microdilution method for C. neoformans and C. gattii against voriconazole and flucytosine. The limitation regarding fluconazole testing against C. neoformans documented in VITEK 2 manufacturer's package insert was confirmed.
Base excision repair system targeting DNA adducts of trioxacarcin/LL-D49194 antibiotics for self-resistance
Authors: Chen Xiaorong , Bradley Noah P , Lu Wei , Wahl Katherine L , Zhang Mei , Yuan Hua , Hou Xian-Feng , Eichman Brandt F , Tang Gong-Li
Published: January 2022

Two families of DNA glycosylases (YtkR2/AlkD, AlkZ/YcaQ) have been found to remove bulky and crosslinking DNA adducts produced by bacterial natural products. Whether DNA glycosylases eliminate other types of damage formed by structurally diverse antibiotics is unknown. Here, we identify four DNA glycosylases—TxnU2, TxnU4, LldU1 and LldU5—important for biosynthesis of the aromatic polyketide antibiotics trioxacarcin A (TXNA) and LL-D49194 (LLD), and show that the enzymes provide self-resistance to the producing strains by excising the intercalated guanine adducts of TXNA and LLD. These enzymes are highly specific for TXNA/LLD-DNA lesions and have no activity toward other, less stable alkylguanines as previously described for YtkR2/AlkD and AlkZ/YcaQ. Similarly, TXNA-DNA adducts are not excised by other alkylpurine DNA glycosylases. TxnU4 and LldU1 possess unique active site motifs that provide an explanation for their tight substrate specificity. Moreover, we show that abasic (AP) sites generated from TxnU4 excision of intercalated TXNA-DNA adducts are incised by AP endonuclease less efficiently than those formed by 7mG excision. This work characterizes a distinct class of DNA glycosylase acting on intercalated DNA adducts and furthers our understanding of specific DNA repair self-resistance activities within antibiotic producers of structurally diverse, highly functionalized DNA damaging agents.
The DNA dioxygenase Tet1 regulates H3K27 modification and embryonic stem cell biology independent of its catalytic activity
Authors: Chrysanthou Stephanie , Tang Qin , Lee Joun , Taylor Samuel J , Zhao Yilin , Steidl Ulrich , Zheng Deyou , Dawlaty Meelad M
Published: January 2022

Tet enzymes (Tet1/2/3) oxidize 5-methylcytosine to promote DNA demethylation and partner with chromatin modifiers to regulate gene expression. Tet1 is highly expressed in embryonic stem cells (ESCs), but its enzymatic and non-enzymatic roles in gene regulation are not dissected. We have generated Tet1 catalytically inactive (Tet1m/m) and knockout (Tet1−/−) ESCs and mice to study these functions. Loss of Tet1, but not loss of its catalytic activity, caused aberrant upregulation of bivalent (H3K4me3+; H3K27me3+) developmental genes, leading to defects in differentiation. Wild-type and catalytic-mutant Tet1 occupied similar genomic loci which overlapped with H3K27 tri-methyltransferase PRC2 and the deacetylase complex Sin3a at promoters of bivalent genes and with the helicase Chd4 at active genes. Loss of Tet1, but not loss of its catalytic activity, impaired enrichment of PRC2 and Sin3a at bivalent promoters leading to reduced H3K27 trimethylation and deacetylation, respectively, in absence of any changes in DNA methylation. Tet1−/−, but not Tet1m/m, embryos expressed higher levels of Gata6 and were developmentally delayed. Thus, the critical functions of Tet1 in ESCs and early development are mediated through its non-catalytic roles in regulating H3K27 modifications to silence developmental genes, and are more important than its catalytic functions in DNA demethylation.
Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer
Authors: Long Wei , Zheng Bo-Xin , Li Ying , Huang Xuan-He , Lin Dan-Min , Chen Cui-Cui , Hou Jin-Qiang , Ou Tian-Miao , Wong Wing-Leung , Zhang Kun , Lu Yu-Jing
Published: January 2022

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand–G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.
Association of diuretic use with increased risk for long-term post-transplantation diabetes mellitus in kidney transplant recipients
Authors: Sokooti Sara , Klont Frank , Tye Sok Cin , Kremer Daan , Douwes Rianne M , Hopfgartner Gérard , Dullaart Robin P F , Heerspink Hiddo J L , Bakker Stephan J L
Published: January 2022

Background

Post-transplantation diabetes mellitus (PTDM) is a major clinical problem in kidney transplant recipients (KTRs). Diuretic-induced hyperglycaemia and diabetes have been described in the general population. We aimed to investigate whether diuretics also increase PTDM risk in KTRs.

Methods

We included 486 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Participants were classified as diuretic users and non-users based on their medication use verified by medical records.

Results

At the baseline study, 168 (35%) KTRs used a diuretic (thiazide, n = 74; loop diuretic, n = 76; others, n = 18) and 318 KTRs did not use a diuretic. After 5.2 years [interquartile range (IQR) 4.0‒5.9] of follow up, 54 (11%) KTRs developed PTDM. In Cox regression analyses, diuretic use was associated with incident PTDM, independent of age, sex, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) {hazard ratio [HR] 3.28 [95% confidence interval (CI) 1.84–5.83]; P <0.001}. Further adjustment for potential confounders, including lifestyle, family history of cardiovascular disease, use of other medication, kidney function, transplantation-specific parameters, BMI, lipids and blood pressure did not materially change the association. Moreover, in Cox regression analyses, both thiazide and loop diuretics associated with the development of PTDM, independent of age, sex, FPG and HbA1c [HR 2.70 (95% CI 1.24–5.29); P = 0.012 and HR 5.08 (95% CI 2.49–10.34); P <0.001), respectively].

Conclusions

This study demonstrates that diuretics overall are associated with an increased risk of developing PTDM in KTRs, independent of established risk factors for PTDM development. The association was present for both thiazide and loop diuretics.
CONVINCE in the context of existing evidence on haemodiafiltration
Authors: Vernooij Robin W M , Bots Michiel L , Strippoli Giovanni F M , Canaud Bernard , Cromm Krister , Woodward Mark , Blankestijn Peter J ,   CONVINCE scientific committee, Davenport Andrew , Canaud Bernard , Barth Claudia , Strippoli Giovanni , Hegbrant Jörgen , Fischer Kathrin , Cromm Krister , Török Mariëtta , Woodward Mark , Rose Matthias , Bots Michiel
Published: January 2022

Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of ‘the comparison of high-dose HDF with high-flux HD’ (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease.
Kidney injury rates after unilateral nephrectomy in childhood—a systematic review and meta-analysis
Authors: Groen in ‘t Woud Sander , Gobino Alessandro , Roeleveld Nel , van den Heuvel Lambert P W J , Feitz Wout F J , van der Zanden Loes F M , Schreuder Michiel F
Published: January 2022

Background

Unilateral nephrectomy is a relatively common procedure in children which results in a solitary functioning kidney (SFK). Living with an SFK predisposes to kidney injury, but it remains unknown which children are most at risk. We aimed to investigate kidney injury rates in patients who underwent unilateral nephrectomy in childhood and to investigate differences among nephrectomies performed for a congenital anomaly, malignancy or other condition.

Methods

MEDLINE and EMBASE were searched for studies reporting kidney injury rates [i.e. proteinuria, hypertension and/or a decreased glomerular filtration rate (GFR)] of patients who underwent unilateral nephrectomy during childhood. Studies including five or more patients with at least 12 months of follow-up were eligible. Analyses were performed using random effects models and stratified by indication for nephrectomy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were used for reporting.

Results

Over 5000 unique articles were screened, of which 53 studies reporting on >4000 patients were included in the analyses. Proteinuria, hypertension and a decreased GFR were present in 15.3, 14.5 and 11.9% of patients, respectively. Heterogeneity among the studies was large in several subgroups, impairing quantitative meta-analyses. However, none of our analyses indicated differences in injury rates between a congenital anomaly or malignancy as an indication for nephrectomy.

Conclusions

Unilateral nephrectomy during childhood results in signs of kidney injury in >10% of patients, with no clear difference between the indications for nephrectomy. Therefore, structured follow-up is necessary in all children who underwent nephrectomy, regardless of the indication.
Effects of Prenatal Nicotine, THC, or Co-Exposure on Cognitive Behaviors in Adolescent Male and Female Rats
Authors: Lallai Valeria , Manca Letizia , Sherafat Yasmine , Fowler Christie D
Published: January 2022

Introduction

Although there has been a decrease in the prevalence of tobacco smoking, exposure to nicotine during pregnancy remains a substantial problem worldwide. Further, given the recent escalation in e-cigarette use and legalization of cannabis, it has become essential to understand the effects of nicotine and cannabinoid co-exposure during early developmental stages.

Aims and Methods

We systematically examined the effects of nicotine and/or THC prenatal exposure on cognitive behaviors in male and female offspring. Dams were exposed to nicotine vape or vehicle, and oral edible THC or vehicle, throughout pregnancy. Adolescent offspring were then tested in the prepulse inhibition test, novel object recognition task, and novelty suppressed feeding task.

Results

At birth, pups from mothers exposed to nicotine vape or oral THC exhibited reduced body weight, compared to control pups. Prenatal nicotine vape exposure resulted in a decreased baseline startle reactivity in adolescent male and female rats, and in females, enhanced sensorimotor gating in the prepulse inhibition test. Prenatal nicotine and THC co-exposure resulted in significant deficits in the prepulse inhibition test in males. Deficits in short-term memory were also found in males prenatally exposed to THC, either alone or with nicotine co-exposure, and in females exposed to THC alone. Finally, in males, a modest increase in anxiety-associated behaviors was found with THC or nicotine exposure in the latency to approach a novel palatable food.

Conclusions

These studies demonstrate differential effects of prenatal exposure to e-cigarette nicotine vape and/or edible THC on cognitive function, with differing effects within male and female groups.

Implications

These studies demonstrate an impact of nicotine, THC, or co-exposure during early developmental stages in utero on behavioral outcomes in adolescence. These findings have important translational implications given the continued use of nicotine and THC containing products by pregnant women worldwide, which can be applied to support healthcare and policy efforts restricting nicotine and THC use during pregnancy.
The unexpected influencer: Pope Francis and European perceptions of the recent refugee crisis
Authors: Deiana Claudio , Mazzarella Gianluca , Meroni Elena Claudia , Tiozzo Pezzoli Luca
Published: January 2022

This article analyses the impact of non-informative communication on Europeans’ perceptions of European Union (EU) action on the issue of migration. We exploit the fact that Pope Francis’s visit to Lesbos Island in 16 April 2016, overlaps with the days of the interviews for a Special Eurobarometer survey, such that some respondents were unintentionally exposed to the Pope’s speech while others were not. Comparing Catholics and non-Catholics before and after the Pope’s visit in a difference-in-differences setting, we show that the papal message persuaded exposed Catholic individuals that EU action on the issue of migration is insufficient. The effect is temporary and varies according to the demographic characteristics of the respondents and by the country’s share of asylum applicants in 2015. Moreover, media exposure of the Pope’s visit, measured by the Global Database of Events, Language, and Tone, was greater in Catholic countries, and this might explain the effect found.
Feminist Institutional Change: The Case of the UK Women and Equalities Committee
Authors: Childs Sarah
Published: January 2022

The UK Government’s decision to establish the Women and Equalities Committee in 2015 redressed an institutional deficit at Westminster—the lack of a Departmental Select Committee holding the Women’s Minister and Government Equalities Office to account. This ‘effective’ reform was by no means a foregone conclusion, however. A feminist institutionalist (FI) approach demonstrates the limitations of traditional accounts of institutional change in accounting for this reform. With greater analytical space given to women’s agency and introducing the concept of gendered parliamentarianism, FI captures the gendered constraints and conducive conditions that marked this moment of parliamentary re-gendering: identifying the critical role of women MPs; the new relations between them and women parliamentary Clerks and officials and the wider—crucially gendered—(extra) parliamentary actors and dynamics in play.
The Xanthomonas type-III effector XopS stabilizes CaWRKY40a to regulate defense responses and stomatal immunity in pepper (Capsicum annuum)
Authors: Raffeiner Margot , Üstün Suayib , Guerra Tiziana , Spinti Daniela , Fitzner Maria , Sonnewald Sophia , Baldermann Susanne , Börnke Frederik
Published: January 2022

As a critical part of plant immunity, cells that are attacked by pathogens undergo rapid transcriptional reprogramming to minimize virulence. Many bacterial phytopathogens use type III effector (T3E) proteins to interfere with plant defense responses, including this transcriptional reprogramming. Here, we show that Xanthomonas outer protein S (XopS), a T3E of Xanthomonas campestris pv. vesicatoria (Xcv), interacts with and inhibits proteasomal degradation of WRKY40, a transcriptional regulator of defense gene expression. Virus-induced gene silencing of WRKY40 in pepper (Capsicum annuum) enhanced plant tolerance to Xcv infection, indicating that WRKY40 represses immunity. Stabilization of WRKY40 by XopS reduces the expression of its targets, which include salicylic acid-responsive genes and the jasmonic acid signaling repressor JAZ8. Xcv bacteria lacking XopS display significantly reduced virulence when surface inoculated onto susceptible pepper leaves. XopS delivery by Xcv, as well as ectopic expression of XopS in Arabidopsis thaliana or Nicotiana benthamiana, prevented stomatal closure in response to bacteria and biotic elicitors. Silencing WRKY40 in pepper or N. benthamiana abolished XopS’s ability to prevent stomatal closure. This suggests that XopS interferes with both preinvasion and apoplastic defense by manipulating WRKY40 stability and downstream gene expression, eventually altering phytohormone crosstalk to promote pathogen proliferation.
Correlation of vacuole morphology with stomatal lineage development by whole-cell electron tomography
Authors: Cao Wenhan , Li Zhenping , Huang Shuxian , Shi Yuwei , Zhu Ying , Lai Man Nga , Lok Pui Lok , Wang Xiangfeng , Cui Yong , Jiang Liwen
Published: January 2022

Stomatal movement is essential for plants to optimize transpiration and therefore photosynthesis. Rapid changes in the stomatal aperture are accompanied by adjustment of vacuole volume and morphology in guard cells (GCs). In Arabidopsis (Arabidopsis thaliana) leaf epidermis, stomatal development undergoes a cell-fate transition including four stomatal lineage cells: meristemoid, guard mother cell, young GC, and GC. Little is known about the mechanism underlying vacuole dynamics and vacuole formation during stomatal development. Here, we utilized whole-cell electron tomography (ET) analysis to elucidate vacuole morphology, formation, and development in different stages of stomatal lineage cells at nanometer resolution. The whole-cell ET models demonstrated that large vacuoles were generated from small vacuole stepwise fusion/maturation along stomatal development stages. Further ET analyses verified the existence of swollen intraluminal vesicles inside distinct vacuoles at certain developmental stages of stomatal lineage cells, implying a role of multivesicular body fusion in stomatal vacuole formation. Collectively, our findings demonstrate a mechanism mediating vacuole formation in Arabidopsis stomatal development and may shed light on the role of vacuoles in stomatal movement.
An update on precision genome editing by homology-directed repair in plants
Authors: Chen Jilin , Li Shaoya , He Yubing , Li Jingying , Xia Lanqin
Published: January 2022

Beneficial alleles derived from local landraces or related species, or even orthologs from other plant species, are often caused by differences of one or several single-nucleotide polymorphisms or indels in either the promoter region or the encoding region of a gene and often account for major differences in agriculturally important traits. Clustered regularly interspaced short palindromic repeats-associated endonuclease Cas9 system (CRISPR/Cas9)-mediated precision genome editing enables targeted allele replacement or insertion of flag or foreign genes at specific loci via homology-directed repair (HDR); however, HDR efficiency is low due to the intrinsic rare occurrence of HDR and insufficient DNA repair template in the proximity of a double-stranded break (DSB). Precise replacement of the targeted gene with elite alleles from landraces or relatives into a commercial variety through genome editing has been a holy grail in the crop genome editing field. In this update, we briefly summarize CRISPR/Cas-mediated HDR in plants. We describe diverse strategies to improve HDR efficiency by manipulating the DNA repair pathway, timing DSB induction, and donor delivery, and so on. Lastly, we outline open questions and challenges in HDR-mediated precision genome editing in both plant biological research and crop improvement.
Antilocution and trust in the workplace: Perceptions of higher education trained police recruits in England and Wales
Authors: Rogers Colin , Turner James , Birch Philip
Published: January 2022

This study seeks to examine the relationship between antilocution and trust in the workplace by reflecting on the perceptions of police officers who are undertaking the new Higher Education (HE) pathway into the policing profession in England and Wales. This relationship is considered through Allport (1979). ‘The Nature of Prejudice. New York, NY: Perseus’ concept of antilocution and the lens of trust in the workplace, to understand how new police students think they are regarded by their policing colleagues and its impact on practice. Utilizing a survey of police students from five different forces in England and Wales, indicative results suggest that, whilst broadly supportive of new police officers, there may be some division regarding their education and training pathway through higher education, engendering levels of prejudice and bias towards the new recruits. Police student responses indicate that many of them feel that more is expected of them and that they are under closer supervision because they have undertaken the Higher Education route. Arguably, this prejudice and bias have an adverse effect on trust within the workplace, a concept which is front and centre of policing which ultimately can have a negative impact on public safety and security. The results of this study indicate that the interaction between new recruits (out-group) and established colleagues (in-group) is complex and not straightforward, and suggested implications for police practice are presented.
Short Selling ETFs
Authors: Li Frank Weikai , Zhu Qifei
Published: January 2022

We provide novel evidence that arbitrageurs use exchange-traded funds (ETFs) as an avenue to circumvent short-sale constraints at the stock level. Using a large sample of U.S. equity ETF holdings, we document that shorting activity on ETFs rises with the difficulty of shorting underlying stocks. Stocks heavily shorted via their holding ETFs underperform those that are lightly shorted. The return predictability of ETF shorting is distinct from stock-level shorting measures and is concentrated among stocks that face severe arbitrage constraints. These findings suggest that ETFs allow arbitrageurs to target overpriced stocks that are otherwise difficult to short. (JEL G12, G14)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Carbamylation of β2-glycoprotein I generates new autoantigens for antiphospholipid syndrome: a new tool for diagnosis of ‘seronegative’ patients
Authors: Capozzi Antonella , Truglia Simona , Buttari Brigitta , Recalchi Serena , Riitano Gloria , Manganelli Valeria , Mancuso Silvia , Alessandri Cristiano , Longo Agostina , Mattei Vincenzo , Profumo Elisabetta , Garofalo Tina , Misasi Roberta , Conti Fabrizio , Sorice Maurizio
Published: January 2022

Objectives

Antiphospholipid syndrome (APS) is a prothrombotic condition defined by recurrent thrombosis, pregnancy complications and circulating antiphospholipid antibodies (aPL), including anti-β2-glycoprotein I (β2-GPI). In clinical practice it is possible to find patients with APS persistently negative for the aPL tests according to Sydney criteria (‘seronegative APS’, SN-APS). Recently, several autoimmune responses have been described as a consequence of post-translational modifications of their target autoantigens. This study was undertaken to test carbamylated-β2-GPI (Carb-β2-GPI) as a new autoantigen of APS.

Methods

β2-GPI was carbamylated by potassium cyanate and used to investigate its effect on monocyte-derived dendritic cell (moDC) phenotype and function. Sera from 114 SN-APS patients, 60 APS, 20 patients with RA, 20 non-APS thrombosis and 50 healthy donors were analysed for anti-Carb-β2-GPI by ELISA.

Results

Carb-β2-GPI is able to activate moDCs, inducing upregulation of CD80, CD86 and CD40, activation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and nuclear factor-κB, and IL-12p70 release. Serological results showed that both 37/114 SN-APS (32.46%) and 23/60 APS (38.33%) patients resulted positive for anti-Carb-β2-GPI. Interestingly, SN-APS patients who tested positive for anti-Carb-β2-GPI showed a higher prevalence of thrombocytopenia (P = 0.04, likelihood positive ratio of 3.9).

Conclusion

Data obtained from both functional tests on moDCs and immunological approaches prompted identification of Carb-β2-GPI as a ‘new’ antigenic target in APS. In particular, anti-Carb-β2-GPI revealed a potential usefulness in identification of a significant proportion of SN-APS patients. Moreover, since patients who tested positive for anti-Carb-β2-GPI reported a high risk of thrombocytopenia, this test may be considered a suitable approach in the clinical evaluation of SN-APS.
Effective connectivity of the human mirror neuron system during social cognition
Authors: Sadeghi Sadjad , Schmidt Stephanie N L , Mier Daniela , Hass Joachim
Published: January 2022

The human mirror neuron system (MNS) can be considered the neural basis of social cognition. Identifying the global network structure of this system can provide significant progress in the field. In this study, we use dynamic causal modeling (DCM) to determine the effective connectivity between central regions of the MNS for the first time during different social cognition tasks. Sixty-seven healthy participants completed fMRI scanning while performing social cognition tasks, including imitation, empathy and theory of mind. Superior temporal sulcus (STS), inferior parietal lobule (IPL) and Brodmann area 44 (BA44) formed the regions of interest for DCM. Varying connectivity patterns, 540 models were built and fitted for each participant. By applying group-level analysis, Bayesian model selection and Bayesian model averaging, the optimal family and model for all experimental tasks were found. For all social-cognitive processes, effective connectivity from STS to IPL and from STS to BA44 was found. For imitation, additional mutual connections occurred between STS and BA44, as well as BA44 and IPL. The results suggest inverse models in which the motor regions BA44 and IPL receive sensory information from the STS. In contrast, for imitation, a sensory loop with an exchange of motor-to-sensory and sensory-to-motor information seems to exist.
Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia
Authors: Davidson Michael , Saoud Jay , Staner Corinne , Noel Nadine , Werner Sandra , Luthringer Elisabeth , Walling David , Weiser Mark , Harvey Philip D , Strauss Gregory P , Luthringer Remy
Published: January 2022

Background

This is a placebo-controlled multi-national trial of roluperidone, a compound with antagonist properties for 5-HT2A, sigma2, and α1A-adrenergic receptors, targeting negative symptoms in patients with schizophrenia. This trial follows a previous trial that demonstrated roluperidone superiority over placebo in a similar patient population.

Methods

Roluperidone 32 mg/day, roluperidone 64 mg/day, or placebo was administered for 12 weeks to 513 patients with schizophrenia with moderate to severe negative symptoms. The primary endpoint was the PANSS-derived Negative Symptom Factor Score (NSFS) and the key secondary endpoint was Personal and Social Performance scale (PSP) total score.

Results

NSFS scores were lower (improved) for roluperidone 64 mg compared to placebo and marginally missing statistical significance for the intent-to-treat (ITT) analysis data set (P ≤ .064), but reached nominal significance (P ≤ .044) for the modified-ITT (m-ITT) data set. Changes in PSP total score were statistically significantly better on roluperidone 64 mg compared to placebo for both ITT and m-ITT (P ≤ .021 and P ≤ .017, respectively).

Conclusions

Results of this trial confirm the potential of roluperidone as a treatment of negative symptoms and improving everyday functioning in patients with schizophrenia. Study registration: Eudra-CT: 2017-003333-29; NCT03397134.
Local political turnover, R&D investment leap and corporate innovation performance: Evidence from China
Authors: Jiang Zhenyu , Wang Zongjun , Feng Chengxiao , Yi Lin
Published: January 2022

This study explores how local political turnover affects corporate R&D investment and innovation performance in an emerging economy like China. Based on the panel data of 956 listed firms in China, we found that local officials’ turnover has a direct negative effect on both R&D investment leap and corporate innovation performance. Furthermore, local officials’ turnover inhibits innovation performance provided the new officials are transferred from other places but improves innovation performance provided the old officials are dismissed for corruption or other violations. Finally, R&D investment leap positively moderate the relationship between local officials’ turnover and corporate innovation performance. These findings contribute to the literature on how political uncertainty at the regional level affects R&D and innovation activities at the firm level and provide significant guidance for both the government and manufacturers in China.
What counts: Making sense of metrics of research value
Authors: Williams Kate
Published: January 2022

There is no singular way of measuring the value of research. There are multiple criteria of evaluation given by different fields, including academia but also others, such as policy, media, and application. One measure of value within the academy is citations, while indications of wider value are now offered by altmetrics. This study investigates research value using a novel design focusing on the World Bank, which illuminates the complex relationship between valuations given by metrics and by peer review. Three theoretical categories, representing the most extreme examples of value, were identified: ‘exceptionals’, highest in both citations and altmetrics; ‘scholars’, highest in citations and lowest in altmetrics; and ‘influencers’, highest in altmetrics and lowest in citations. Qualitative analysis of 18 interviews using abstracts from each category revealed key differences in ascribed characteristics and judgements. This article provides a novel conception of research value across fields.
Magnitude of SARS-CoV-2 Infection and Outcome in Paediatric Surgical Inpatients during the First Wave of Pandemic at a Tertiary Care Children’s Hospital in India
Authors: Prajapati Sahaj , Choudhury Subhasis Roy , Aditya M , Maheshwari Anu , Anirudha Abhay J , Sarin Yogesh Kumar
Published: January 2022

This study was conducted at a tertiary care centre of Delhi, to assess the magnitude of SARS-CoV-2 disease and outcome in paediatric surgical inpatients. All the admitted patients were evaluated excluding outpatients and minor procedures. Out of 312 operated patients 2.88% patients were SARS-CoV-2 positive and out of 167 non-operative patients 6.58% were SARS-CoV-2 positive. These patients received standard care as per guidelines using standard protective measures and were discharged home. Only 1 death occurred due to perforation peritonitis with sepsis. The overall prevalence of SARS-CoV-2 in paediatric surgical patients was 4.17% and SARS-CoV-2 positive patients had similar outcomes as compared to non-SARS-CoV-2 patients.
Genetic Diversity of Aspergillus flavus Associated with Chili in Nigeria and Identification of Haplotypes with Potential in Aflatoxin Mitigation
Authors: Singh Pummi , Mehl Hillary L. , Orbach Marc J. , Callicott Kenneth A. , Cotty Peter J.
Published: January 2022

Dried red chili (Capsicum spp.), a widely produced and consumed spice in Nigeria, is often contaminated by aflatoxins. Aflatoxins are potent mycotoxins of severe health and economic concern worldwide. Aspergillus flavus often contaminates crops with aflatoxins in warm regions; however, not all isolates are aflatoxin producers. Nonaflatoxigenic isolates have potential as biocontrol agents for aflatoxin mitigation. The current study examined the genetic diversity of A. flavus (n = 325) associated with chilies in Nigeria and identified 123 nonaflatoxigenic isolates. The Nigerian A. flavus isolates from chili were diverse at 17 microsatellite loci, with 5 to 36 alleles per locus, and included 152 haplotypes. The isolates that are active ingredients in Aflasafe, registered for aflatoxin biocontrol on maize and groundnuts in Nigeria, did not share haplotypes with the chili isolates. Of the 152 haplotypes, 65% produced aflatoxins in autoclaved maize, some of which (17%) produced >100,000 µg/kg of aflatoxins. Aflatoxins were not detected in 35% of the haplotypes. Cluster amplification pattern assay detected large deletions in the aflatoxin biosynthetic clusters of some (32%) of the nonaflatoxigenic haplotypes. Coinfection of chili with nonaflatoxigenic isolates from chilies (n = 7) and A. aflatoxiformans resulted in a significantly greater average reduction in total aflatoxins compared with that achieved by Aflasafe active ingredient isolates (P < 0.01). These nonaflatoxigenic isolates are a genetic resource for the development of biological control products for aflatoxin mitigation in chilies in Nigeria and should be evaluated under field conditions.
Impact of Calonectria Diseases on Ornamental Horticulture: Diagnosis and Control Strategies
Authors: Aiello Dalia , Guarnaccia Vladimiro , Vitale Alessandro , LeBlanc Nicholas , Shishkoff Nina , Polizzi Giancarlo
Published: January 2022

Diseases caused by fungi in the genus Calonectria pose a significant threat to the ornamental horticulture industries in Europe and the United States. Calonectria spp. are particularly challenging pathogens to manage in ornamental production systems and the urban landscape for multiple reasons. A high level of species diversity and poorly resolved taxonomy in the genus makes proper pathogen identification and disease diagnosis a challenge, though recent molecular phylogenetic studies have made significant advances in species delimitation. From a disease management perspective, Calonectria spp. produce long-lived survival structures (microsclerotia) that contaminate nursery production systems and can survive multiple years in the absence of a susceptible plant host. Latent infection of plant material is poorly understood but likely contributes to long-distance dissemination of these fungal pathogens, including the clonal Calonectria spp. responsible for the global emergence of boxwood blight. Breeding for disease resistance represents a sustainable strategy for managing Calonectria diseases but is challenging due to the perennial nature of many ornamental plants and high levels of susceptibility in commercial cultivars. Ultimately, long-term sustainable management of Calonectria diseases will require an improved understanding of pathogen biology as well as integration of multiple disease management strategies.
Angiotensin-Converting Enzyme 2 Expression Is Detectable in Keratinocytes, Cutaneous Appendages, and Blood Vessels by Multiplex RNA In Situ Hybridization
Authors: Ganier Clarisse , Harun Nasrat , Peplow Imogen , Du-Harpur Xinyi , Arthurs Callum , Watt Fiona M. , Lynch Magnus D.
Published: January 2022

OBJECTIVE

The angiotensin-converting enzyme 2 (ACE2) receptor mediates uptake of SARS-CoV-2, the virus responsible for COVID-19. Previous work analyzing publicly available bulk RNA-sequencing data sets has shown the expression of ACE2 in human keratinocytes. This finding is potentially relevant for the etiology of COVID-19-associated rashes and might also suggest a possible entry mechanism for the SARS-CoV-2 virus. In this study, the authors examined the spatial localization of ACE2 mRNA in vivo.

METHODS AND RESULTS

The authors analyzed several publicly available single-cell RNA-sequencing data sets. They determined spatial localization of ACE2 mRNA using multiplex RNA in situ hybridization in human skin.

CONCLUSIONS

Both analyses supported ACE2 expression in keratinocytes and skin vasculature, which could reflect a potential cutaneous entry point for SARS-CoV-2, particularly in damaged or broken skin. Moreover, ACE2 expression in vascular endothelial cells may support direct, virally mediated mechanisms in the etiology of the chilblain-like acral eruption that is seen in patients with COVID-19.
Resilience Will Not Erase Structural Racism
Authors: Rumala Bernice B. , Beard Kenya V.
Published: January 2022

Acknowledging underlying inequities is crucial.
The Beauty in Breaking and the Power to Heal
Authors: Brown Theresa
Published: January 2022

Michele Harper's striking memoir contextualizes racism in health care.
No Negative Association Between Sun Protection and Bone Health
Authors: Rosenberg Karen
Published: January 2022

According to this study:

The practice of sun protection is not associated with bone-related health complications, such as an increased risk of osteoporotic fractures.

Sun protection should be encouraged for all patients, including those at risk for decreased bone mineral density and fractures.
Self-Monitoring of Blood Glucose Can Lead to Improved Glycemic Control
Authors: Rosenberg Karen
Published: January 2022

According to this study:

In non-insulin-treated patients who have type 2 diabetes, structured self-monitoring of blood glucose leads to clinically significant improvements in glycated hemoglobin.

Patients with suboptimal glycemic control derive the most benefit from self-monitoring.
Case–Control Studies
Authors: Keeler Courtney , Curtis Alexa Colgrove
Published: January 2022

Editor's note: This is the eighth article in a series on clinical research by nurses. The series is designed to give nurses the knowledge and skills they need to participate in research, step by step. Each column will present the concepts that underpin evidence-based practice—from research design to data interpretation. The articles will be accompanied by a podcast offering more insight and context from the authors. To see all the articles in the series, go to https://links.lww.com/AJN/A204.
Acute ischemic stroke or migraine with aura? Triage considerations
Authors: Collins-Yoder Angela , Key Betty
Published: January 2022

This article discusses the complex relationship between acute ischemic stroke and migraine with aura, and critical nursing interventions.