bluuebunny/crossref_metadata_2025 huggingface dataset:
circEZH2E2/E3 is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression
Authors: Su Zhengzheng , Zhang Mengni , Luo Han , Zhong Jinjing , Tan Junya , Xu Yunyi , Pan Xiuyi , Zeng Hao , Nie Ling , Xu Miao , Chen Ni , Chen Xueqin , Zhou Qiao
Published: December 2022

The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2. It was not known whether EZH2 itself generates circRNAs that promote its own expression. We here report the identification of circEZH2E2/E3 that is derived from exons 2 and 3 of the EZH2 gene and overexpressed in PCa. We show that circEZH2E2/E3 functions as a dual inhibitor for both miR363 and miR708 that target the EZH2 3′UTR and CDS, respectively, resulting in the upregulation of EZH2 expression and hence the downregulation of EZH2‐repressed genes (e.g., CDH1 and DAB2IP), and enhancement of PCa cell proliferation, migration, invasion, and xenograft PCa growth. Overexpression of circEZH2E2/E3 is significantly correlated with higher tumor grade, tumor progression, and unfavorable progression‐free and disease‐specific survival in PCa patients. These findings show a novel autoenhancing EZH2–circEZH2E2/E3‐miR363/miR708–EZH2 regulatory loop, by which circEZH2E2/E3 plays important roles in PCa tumorigenesis and progression by upregulating EZH2, and may have potential diagnostic, prognostic, and therapeutic uses in PCa management.
Development and use of theory of mind in social and cultural context
Authors: Selcuk Bilge , Gonultas Secil , Ekerim‐Akbulut Muge
Published: December 2022

Theory of mind (ToM) is a key social‐cognitive skill that allows individuals to understand and attribute mental states to others; it facilitates relationships and helps individuals navigate the social world. Thus, it is likely influenced by social and cultural contexts. In this article, we review studies that examine the potential ways through which sociocultural context interacts with the development and use of ToM in Western and non‐Western societies. First, we summarize findings documenting the link between culture and timing of ToM acquisition. Second, we examine cross‐cultural studies on how culture can be related to the sequential development of different dimensions of ToM. Third, we discuss when and how cultural group membership of the targets influences the use of ToM. Finally, we suggest avenues for research so the field can understand more comprehensively the dynamic interactions between sociocultural context and the development and use of ToM.
Soil disturbance impacts on ant‐diaspore multilayer networks in a tropical savanna
Authors: Coelho Paula Grandi L. , Antonini Yasmine , da Costa Fernanda Vieira
Published: December 2022

1. Current anthropogenic disturbances have changed natural environments, broadly impacting ecosystem services and functions. Here, the authors focused on the secondary dispersal of diaspores by ants, which serve an important ecological function in the natural regeneration of degraded habitats.

2. The authors experimentally studied the effects of vegetation suppression and soil disturbance on (i) diaspore removal, (ii) the quality of secondary removal, and (iii) the structure of interaction networks between ants and diaspores. The authors tested whether the disturbance affected the species richness of seed removers, diaspore removal rate, removal distance and time, and removal effectiveness. Additionally, the authors tested whether the structure of ant‐diaspore networks, that is, specialisation, modularity and robustness, is altered by soil disturbance. To do that, the authors studied three degraded and three preserved areas in the Brazilian Cerrado.

3. The authors observed 25 ant species interacting with the diaspores. Disturbance did not affect ant species richness, removal distance or removal rate, but ants took twice as long to remove the diaspores in the preserved habitat. The frequency of interaction networks was higher in the preserved habitat, and the effectiveness of species in removing the diaspores differed between habitats. Surprisingly, the authors observed that ants considered effective dispersers mostly occurred in degraded habitats, highlighting the potential of myrmecochory in the regeneration of impacted environments.

4. The findings point to the potential of ants in acting as secondary seed dispersal, improving the restoration of areas highly impacted by soil disturbance. Moreover, this study contributes to understanding the effects of anthropogenic disturbances on ecological interactions and ecosystem functions.
Effectiveness of endodontic complexity assessment tool (E‐CAT) on the undergraduate students in an endodontic training program and its predictive capability on complications
Authors: Hatipoğlu Fatma Pertek , Akıncı Levent
Published: December 2022

Introduction

Dental students face a number of challenges when it comes to performing root canal treatments (RCTs). The Endodontic Complexity Assessment Tool (E‐CAT) was developed to assist dental practitioners in assessing the complexity of RCTs before beginning treatment.

Materials and Methods

The E‐CAT was filled out independently by both the educator and the student. To allow educators to record scores and complexity classes, they transferred their and students' forms to the website https://www.e‐cat.uk/. Students began endodontic treatment after learning about the complexity level of the case. The educators were responsible for recording any complications encountered in every case from the outset to 1 month after treatment.

Results

A total of 70 students, 33 in fourth and 37 in fifth‐grade, were included in the study. In the cases with higher E‐CAT scores, complications such as misdiagnosed, faulty access cavity, furca or coronal third perforation, insufficient root canal instrumentation, working length loss, canal blockage, overpreparation, incomplete root canal filling and overfilling were experienced significantly more often compared to the cases with lower E‐CAT scores (p < .05). The number of complications (r = .40, p < .001), treatment sessions (r = .44, p < .001), and teacher support (r = .24, p < .001) positively correlated with E‐CAT score (p < .05).

Conclusion

The E‐CAT is an effective tool for assisting dental students in understanding technical challenges, such as complex root canal anatomy and possible complications during treatment. Educators can also use e‐CAT to pre‐select clinical cases and standardise student training by offering cases of equal complexity.
Clinical experience of undergraduate dental students in paediatric dentistry: A 5‐year cross‐sectional study
Authors: Leith Rona , Olegário Isabel Cristina , O'Connell Anne C.
Published: December 2022

Introduction

The clinical experience of undergraduate dental students in Paediatric Dentistry has a profound influence on their future confidence. The purpose of this study was to evaluate the clinical experience of undergraduate students in Paediatric Dentistry over five consecutive years and to determine whether changes in teaching practices are reflected in the clinic.

Materials and Methods

In total, 196 records submitted at the end of the Paediatric Dentistry training from the last 5 years (2016–2020) were evaluated. The variables analysed included the number of patients treated per student, the year, and the numbers and types of procedures performed individually across the years. The data were grouped into two categories; pre and post implementation of an electronic portfolio and a change in teaching practices (2016–2017 and 2018–2020 respectively). Data were analysed using Student's t‐test or Mann–Whitney for two group comparison, depending on data distribution (α = 5%).

Results

There was a significant reduction in the number of radiographs exposed (p = .013) between the two groups. The number of fissure sealants had increased in recent years (p < .001). Although the number of stainless steel crowns performed remained unchanged (p = .98), there was an increase in the number of crowns placed using the Hall technique (p < .001) and a concurrent decrease in the number of conventional crowns placed (p < .001).

Conclusion

The clinical experience of undergraduate students has changed in line with evolving teaching practices. The use of objective measures such as patient numbers and range of procedures can be used as a method of evaluating student clinical experience. Other assessment tools are still required to evaluate additional aspects of clinical learning in paediatric dentistry.
Increasing aridity causes larger and more severe forest fires across Europe
Authors: Grünig Marc , Seidl Rupert , Senf Cornelius
Published: December 2022

Area burned has decreased across Europe in recent decades. This trend may, however, reverse under ongoing climate change, particularly in areas not limited by fuel availability (i.e. temperate and boreal forests). Investigating a novel remote sensing dataset of 64,448 fire events that occurred across Europe between 1986 and 2020, we find a power‐law relationship between maximum fire size and area burned, indicating that large fires contribute disproportionally to fire activity in Europe. We further show a robust positive correlation between summer vapor pressure deficit and both maximum fire size (R2 = .19) and maximum burn severity (R2 = .12). Europe's fire regimes are thus highly sensitive to changes in future climate, with the probability for extreme fires more than doubling by the end of the century. Our results suggest that climate change will challenge current fire management approaches and could undermine the ability of Europe's forests to provide ecosystem services to society.
TAIL FORECASTING WITH MULTIVARIATE BAYESIAN ADDITIVE REGRESSION TREES
Authors: Clark Todd E. , Huber Florian , Koop Gary , Marcellino Massimiliano , Pfarrhofer Michael
Published: December 2022

We develop multivariate time‐series models using Bayesian additive regression trees that posit nonlinearities among macroeconomic variables, their lags, and possibly their lagged errors. The error variances can be stable, feature stochastic volatility, or follow a nonparametric specification. We evaluate density and tail forecast performance for a set of U.S. macroeconomic and financial indicators. Our results suggest that the proposed models improve forecast accuracy both overall and in the tails. Another finding is that when allowing for nonlinearities in the conditional mean, heteroskedasticity becomes less important. A scenario analysis reveals nonlinear relations between predictive distributions and financial conditions.
Dynamic compressive response and fracture mechanisms of ZrB2–SiC ceramic based on discrete element method
Authors: Wang Mi , Chen Xiaobin , Xie Guoqing , Wang Lingling , Yu Zhaosheng , Wang Fengdong
Published: December 2022

To investigate the dynamic compression behaviors of fracturing and damage evolution of ZrB2–SiC ceramic, this paper proposes a discrete element method to carry out the dynamic compressive behavior of ZrB2–SiC ceramic. This study is based on three‐dimensional discrete element‐finite difference coupling modeling to realize the reproduction of the splitting Hopkinson pressure bar experiment process. Micro‐parameters of the linear parallel bond model are obtained by calibrating dynamic compression strengths, stress–strain curves, and fracture characteristics of ZrB2–SiC ceramic. The dynamic compressive stress–strain curve can be divided into four stages according to the microcrack evolution and acoustic emission: stage I, linear elastic stage; stage II, microcrack initiation and then stable development stage; stage III, increment stage of microcracks before peak strength; stage IV, increment stage of microcracks after peak strength. The dynamic damage evolution with strain shows a Weibull distribution. The shape and scale parameters change with strain rate. In addition, under the dynamic compression, crack initiation stress, fracture pattern, and fragment size distribution of the ZrB2–SiC ceramic composite exhibited a significant strain‐rate dependence.
An efficient combination immunotherapy for antitumor immunity without accelerating cardiac allograft rejection
Authors: Miao Xiaolong , Wu Zelai , Jiang Yuancong , Liu Han , Gong Weihua
Published: December 2022

Immunotherapy with immune checkpoint inhibitors (ICIs), including antibodies against programmed cell death protein‐1 (PD‐1) and its receptor programmed cell death ligand‐1 (PD‐L1), represents a promising systematic treatment for advanced human malignancies. Transplantation remains the ultimate therapy for end‐stage organ diseases. However, the efficacy of ICI treatment in solid organ transplant (SOT) recipients remains controversial. We established a transgenic primary liver cancer mouse model and performed allogeneic heterotopic heart transplantation. Different treatments were performed and survival curves were calculated. Graft samples were collected, and immune cells and the cell surface expression of PD‐L1 were analysed by flow cytometry. Inflammatory cytokine levels in the serum were measured by an inflammatory array. The specificity of the histochemical techniques was tested by staining sections. A combination immunotherapy comprising a BET protein inhibitor (JQ1) and an immune checkpoint inhibitor (anti‐PD‐L1 antibody) was administered to primary liver cancer model mice bearing cardiac allografts. Interestingly, the combination immunotherapy effectively suppressed the progression of primary liver cancer but did not accelerate allograft rejection. In accordance with our previous findings, BET protein inhibition enhances the expression of a putative membrane transporter (Rab8A), which upregulates the expression of PD‐L1 on the plasma membrane in a transgenic primary liver cancer mouse model. This may be a crucial mechanism of tumour progression arrest. Our data showed that heart transplantation upregulated the expression of the proinflammatory factor IFN‐γ and suggested that BET protein inhibition (with JQ1) decreased PD‐L1 expression in heart tissues after cardiac transplantation. This phenomenon was accompanied by enhanced infiltration of inflammatory IFN‐γ. Our study provides a novel and efficient therapeutic strategy for SOT recipients.
Analysis of defect mechanisms in nonstoichiometric ceria–zirconia by the microwave cavity perturbation method
Authors: Steiner Carsten , Hagen Gunter , Kogut Iurii , Fritze Holger , Moos Ralf
Published: December 2022

In this microwave study, the defect chemistry of ceria–zirconia solid solutions (CZO, Ce1−yZryO2−δ) was investigated at high temperatures by a resonant microwave method. Specifically, the effects of temperature and Zr content on the dielectric properties and defect chemistry mechanisms in CZO were analyzed. Experiments were performed on a series of different CZO powders (y = 0.2, 0.33, 0.50, 0.67). Measurements at 600°C and different oxygen partial pressures (pO2 = 10−26–0.2 bar) confirm a dominant n‐type conduction of small‐polarons in CZO due to the preferred formation of oxygen vacancies, which is also supported by a multimodal analysis. Polarization losses were found to be negligible in the GHz range. Furthermore, an increased relative permittivity was observed in CZO, which correlates with the concentration of oxygen vacancies in CZO. Our microwave study is the first to provide a comprehensive data set for the dielectric properties of CZO powder sample in a wide range of different conditions. In addition, the connection of dielectric properties to CZO defect chemistry mechanisms is presented. The results are in good agreement with findings in the literature and may contribute to a better understanding of microwave‐based state diagnosis of CZO‐based materials, as it discussed for three‐way catalysts.
Superior ferroelectric properties and enhanced depolarization temperature simultaneously achieved in BNT‐based ceramics
Authors: Peng Ping , Li Kunyou , Nie Hengchang , Xiao Xueqing , Zheng Chan , Lin Yezhan , Wang Genshui , Dong Xianlin
Published: December 2022

Bi0.5Na0.5TiO3‐based ceramics with high remnant polarization Pr have shown outstanding potential in the application of high‐power ferroelectric transducers. However, low depolarization temperature Td is an obstacle for their application. Here, a composition design strategy was proposed to simultaneously improve the Td and Pr in BNT‐based materials. Ultrahigh Pr of 40.56 µC/cm2 and relative high Td of 184°C were synergistically achieved in (Bi0.5Na0.5)(Ti0.995Mn0.005)O3 (BNMT) ceramics by adding 1.0 mol% BiGaO3 (BG), which is superior to other reported lead‐free systems. The excellent ferroelectric properties were attributed to strengthen ferroelectric order as evidenced by increased rhombohedral distortion. Meanwhile, the enhanced depolarization temperature, increasing from 168°C for x = 0% to 184°C for x = 1.0%, can be ascribed to the suppression of the thermal‐induced ferroelectric‐relaxor phase transition by adding BG. Those results enable the BNMT‐BG systems ceramics to be an attractive candidate for application in high‐power supplies.
Object neophilia in wild herring gulls in urban and rural locations
Authors: Inzani Emma L. , Kelley Laura A. , Boogert Neeltje J.
Published: December 2022

Living with increasing urbanisation and human populations requires resourcefulness and flexibility in wild animals' behaviour. Animals have to adapt to anthropogenic novelty in habitat structure and resources that may not resemble, or be as beneficial as, natural resources. Herring gulls Larus argentatus increasingly reside in towns and cities to breed and forage, yet how gulls are adjusting their behaviour to life in urban areas is not yet fully understood. This study investigated wild herring gulls' responses to novel and common anthropogenic objects in urban and rural locations. We also examined whether gulls' age influenced their object response behaviour. We found that, out of the 126 individual gulls presented with objects, 34% approached them. This suggests that the majority of targeted gulls were wary or lacked interest in the experimental set‐up. Of the 43 gulls that approached the objects, we found that those tested in urban locations approached more slowly than their rural counterparts. Overall, gulls showed no preference for either novel or common anthropogenic objects, and age did not influence likelihood of approach, approach speed or object choice. Individuals paid most attention to the object they approached first, potentially indicative of individual preferences. Our findings indicated that most herring gulls are not as attracted to anthropogenic objects as anecdotal reports have suggested. Covering up obvious food rewards may thus help mitigate human–gull conflict over anthropogenic food sources.
The effects of block‐based visual and text‐based programming training on students' achievement, logical thinking skills, and motivation
Authors: Saygıner Şenol , Tüzün Hakan
Published: December 2022

Background

Studies on the effectiveness of block‐based environments continue to produce inconsistent results. A strong reason for this is that most studies compare environments that are not equivalent to each other or to the level of learners. Moreover, studies that present evidence of the effectiveness of block‐based environments by comparing equivalent environments are limited.

Objectives

This study aims to scrutinize the effects of programming training to be held in equivalent environments (block‐based and text‐based) with university students who do not have prior programming knowledge and experience on achievement, logical thinking, and motivation.

Methods

The study was conducted by using an experimental pretest‐posttest control group design. The study was conducted with 60 students, the total consisting of 30 students in the experimental group and 30 students in the control group. In the experimental group, block‐based visual programming training with Scratch was conducted and the control group received text‐based programming training with Small Basic. The training was maintained for 10 weeks, for 4 h a week in each group. The programming achievement test, the logical thinking skills test, and the motivation scale were used to collect the data.

Results and Conclusions

The results showed that the use of a block‐based environment in programming training contributed positively to the development of students' logical thinking skills, and motivation for learning programming. In contrast, there was evidence that this training did not make a difference on programming success.

Implications

The findings of the study provided evidence of the effectiveness of block‐based training in comparisons made in equivalent environments. Focusing research on this issue may contribute to the improvement of the current understanding.
Kinetic modeling the survival of Escherichia coli in pickled radish fermentation with different salt concentrations
Authors: Wu Jiale , Yang Li , Wu Zhengyun , Zhang Wenxue
Published: December 2022

The survival of Escherichia coli in pickled radish fermentation with salt concentrations from 2% to 10% was studied kinetically. The results showed that mostly E. coli first underwent 1–2 days of growth, followed by a decline and finally died off after 4–5 days of fermentation. A kinetic model was developed to reveal how the growth and survival of E. coli were affected by acid content, pH value and salt concentration during the pickle fermentation. Model‐based simulations suggested that moderate salt concentration (4%–9%) resulted in shorter survival period of E. coli. Sensitivity analysis showed that the lowest pH value for E. coli growth played the most important role in determining the peak amount and the survival period of E. coli. This study provides a reference for risk assessment and safe production of pickles and other similar fermented vegetables.

Practical Applications

This study provides an appropriate salt concentration range for safer production of pickles. The model developed can be a reference for the kinetic analyses and risk assessments of pickle making and other similar fermentation processes.
Evaluation of financial conflicts of interest and quality of evidence in Japanese gastroenterology clinical practice guidelines
Authors: Murayama Anju , Kamamoto Sae , Murata Nanami , Yamasaki Ryota , Yamada Kohki , Yamashita Erika , Saito Hiroaki , Tanimoto Tetsuya , Ozaki Akihiko
Published: December 2022

Background

Clinical practice guidelines assist healthcare professionals in providing evidence‐based care. However, pharmaceutical companies' financial interests often influence guideline content. This study aimed to elucidate the magnitude of financial ties among Japanese gastroenterology guideline authors and the pharmaceutical industry.

Methods

Using pharmaceutical company disclosed payment data, we evaluated financial conflicts of interest (COI) among Japanese Society of Gastroenterology guideline authors between 2016 and 2021. Additionally, we assessed the evidence quality supporting guideline recommendations and associations with financial COI. Finally, we evaluated author COI management during guideline development against global standards.

Results

Overall, 88.2% (231/262) of guideline authors received a median of $12 968 (interquartile range [IQR]: $1839–$70 374) in payments between 2016 and 2019 for lectures, writings, and consulting. Chairpersons received significantly higher payments (median: $86 444 [IQR: $15 455–$165 679]). Notably, 41 (15.6%) authors had undeclared payments exceeding declaration requirements. Low or very low‐quality evidence supported 41.0% of recommendations. There was a negative association between the median 4‐year payment per author and the proportion of recommendations based on low‐quality evidence (odds ratio: 0.966 [95% confidence interval [95% CI]: 0.945–0.987], P = 0.002) and positive association with moderate‐quality evidence (odds ratio: 1.018 [95% CI: 1.011–1.025], P < 0.001). Still, the Japanese Society of Gastroenterology guideline development process remains less transparent, with insufficient COI policies relative to global standards.

Conclusion

There were extensive financial COI between pharmaceutical companies and guideline authors, and more than 40% of recommendations were based on low‐quality evidence. More rigorous and transparent COI policies for guideline development adhering to global standards are warranted.
Racial inequality in functional trajectories between Black and White U.S. veterans
Authors: Jacobs Josephine C. , Bowling Christopher Barrett , Brown Tyson , Smith Valerie A. , Decosimo Kasey , Wilson Sarah M. , Hastings Susan Nicole , Shepherd‐Banigan Megan , Allen Kelli , Van Houtven Courtney
Published: December 2022

Background

Racial inequality in functional trajectories has been well documented in the U.S. civilian population but has not been explored among Veterans. Our objectives were to: (1) assess how functional trajectories differed for Black and White Veterans aged ≥50 and (2) explore how socioeconomic, psychosocial, and health‐related factors altered the relationship between race and function.

Methods

We conducted a prospective, longitudinal analysis using the 2006–2016 Health and Retirement Study. The study cohort included 3700 Veterans who self‐identified as Black or White, responded to baseline psychosocial questionnaires, and were community‐dwelling on first observation. We used stepwise and stratified linear mixed effects models of biannually assessed functional limitations. The outcome measure was as a count of functional limitations. Race was measured as respondent self‐identification as Black or White. Demographic measures included gender and age. Socioeconomic resources included partnership status, education, income, and wealth. Psychosocial stressors included exposure to day‐to‐day and major discrimination, traumatic life events, stressful life events, and financial strain. Health measures included chronic and mental health diagnoses, smoking, rurality, and use of Veterans Affairs services.

Results

Black Veterans developed functional limitations at earlier ages and experienced faster functional decline than White Veterans between the ages of 50 and 70, with convergence occurring at age 85. Once we accounted for economic resources and psychosocial stressors in multivariable analyses, the association between race and the number of functional limitations was no longer statistically significant. Lower wealth, greater financial strain, and traumatic life events were significantly associated with functional decline.

Conclusions

Health systems should consider how to track Veterans' function earlier in the life course to ensure that Black Veterans are able to get timely access to services that may slow premature functional decline. Providers may benefit from training about the role of economic resources and psychosocial stressors in physical health outcomes.
The fecal bacterial microbiota of healthy and sick newborn foals
Authors: Gomez Diego E. , Wong David , MacNicol Jennifer , Dembek Katarzyna
Published: December 2022

Background

The fecal bacterial microbiota of normal foals and foals with enterocolitis has been characterized using next‐generation sequencing technology; however, there are no reports investigating the gut microbiota in foals hospitalized for other perinatal diseases.

Objective

To describe and compare the fecal bacterial microbiota in healthy and sick foals using next‐generation sequencing techniques.

Animals

Hospitalized (17) and healthy foals (21).

Methods

Case‐control study. Fecal samples were collected from healthy and sick foals on admission. Sick foals were further divided into sick nonseptic (SNS, n = 9) and septic (n = 8) foals. After extraction of DNA, the V4 region of the 16 S rRNA gene was amplified using a PCR assay, and the final product was sequenced with an Illumina MiSeq.

Results

Diversity was significantly lower in healthy than sick foals (P < .05). The bacterial membership (Jaccard index) and structure (Yue & Clayton index) of the fecal microbiota of healthy, septic, and SNS foals were similar (AMOVA, P > .05). Bacterial membership (AMOVA, P = .06) and structure (AMOVA, P = .33) were not different between healthy and sick foals. Enterobacteriaceae, Enterococcus, and Streptococcus were among the 5 more abundant taxa identified in both groups.

Conclusion and Clinical Importance

Higher fecal microbiota diversity in sick than healthy foals might suggest a high exposure to environmental microorganisms or an unstable colonic microbiota. The presence of microorganisms causing bacteremia in foals in a high relative abundance in the feces of foals suggests the intestine might play an essential role in the causation of bacteremia in foals.
The effect of specific learning difficulties on general practice written and clinical assessments
Authors: Botan Vanessa , Williams Nicki , Law Graham R. , Siriwardena Aloysius Niroshan
Published: December 2022

Background

Substantial numbers of medical students and doctors have specific learning difficulties (SpLDs) and failure to accommodate their needs can disadvantage them academically. Evidence about how SpLDs affect performance during postgraduate general practice (GP) specialty training across the different licencing assessments is lacking. We aimed to investigate the performance of doctors with SpLDs across the range of licencing assessments.

Methods

We adopted the social model of disability as a conceptual framework arguing that problems of disability are societal and that barriers that restrict life choices for people with disabilities need to be addressed. We used a longitudinal design linking Multi‐Specialty Assessment (MSRA) records from 2016 and 2017 with their Applied Knowledge Test (AKT), Clinical Skills Assessment (CSA), Recorded Consultation Assessment (RCA) and Workplace Based Assessment (WPBA) outcomes up to 2021. Multivariable logistic regression models accounting for prior attainment and demographics were used to determine the SpLD doctors' likelihood of passing licencing assessments.

Results

The sample included 2070 doctors, with 214 (10.34%) declaring a SpLD. Candidates declaring a SpLD were significantly less likely to pass the CSA (OR 0.43, 95% CI 0.26, 0.71, p = 0.001) but not the AKT (OR 0.96, 95% CI 0.44, 2.09, p = 0.913) or RCA (OR 0.81, 95% CI 0.35, 1.85, p = 0.615). Importantly, they were significantly more likely to have difficulties with WPBA (OR 0.28, 95% CI 0.20, 0.40, p < 0.001). When looking at licencing tests subdomains, doctors with SpLD performed significantly less well on the CSA Interpersonal Skills (B = −0.70, 95% CI −1.2, −0.19, p = 0.007) and the RCA Clinical Management Skills (B = −1.68, 95% CI −3.24, −0.13, p = 0.034).

Conclusions

Candidates with SpLDs encounter difficulties in multiple domains of the licencing tests and during their training. More adjustments tailored to their needs should be put in place for the applied clinical skills tests and during their training.
Diagnostic performance of noncultural methods for central nervous system aspergillosis
Authors: Zhou Ling‐Hong , Zhu Rong‐Sheng , Gong Yan‐Ping , Chen Zhong‐Qing , Luo Yu , Cheng Jia‐Hui , Jiang Ying‐Kui , Zhao Hua‐Zhen , Wang Xuan , Chen Wei‐Jun , Zhu Li‐Ping
Published: December 2022

Background

Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult.

Objectives

We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis.

Methods

In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next‐generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut‐off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis.

Results

Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively.

Conclusions

In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.
A quantitative trait locus conferring flood tolerance to deepwater rice regulates the formation of two distinct types of aquatic adventitious roots
Authors: Lin Chen , Ogorek Lucas León Peralta , Liu Dan , Pedersen Ole , Sauter Margret
Published: December 2022

A key trait conferring flood tolerance is the ability to grow adventitious roots as a response to submergence. The genetic traits of deepwater rice determining the development and characteristics of aquatic adventitious roots (AAR) had not been evaluated.

We used near‐isogenic lines introgressed to test the hypothesis that the impressive shoot elongation ability of deepwater rice linked to quantitative trait loci 1 and 12 also promote the development of AAR.

The deepwater rice genotype NIL‐12 possessed expanded regions at the stem nodes where numerous AAR developed as a response to submergence. Two types (AR1 and AR2) of roots with distinct timing of emergence and large differences in morphological and anatomical traits formed within 3 (AR1) to 7 (AR2) d of submergence. The mechanical impedance provided by the leaf sheath caused AR2 to emerge later promoting thicker roots, higher elongation capacity and higher desiccation tolerance. Upregulation of key genes suggests a joint contribution in activating the meristem in AAR enhancing the development of these in response to submergence.

The morphological and anatomical traits suggested that AR2 is better adapted to long‐term flooding than AR1. We therefore propose that AR2 in deepwater rice functions as an evolutionary defence strategy to tackle periodic submergence.
Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma
Authors: Yamakawa Nobuhiro , Umeda Masahiro , Yoshii Yumi , Mitsudo Kenji , Noguchi Makoto , Kusukawa Jingo , Katakura Akira , Nakayama Hideki , Sasaki Masashi , Noguchi Tadahide , Ueda Michihiro , Bukawa Hiroki , Yagihara Kazuhiro , Horie Akihisa , Miyazaki Akihiro , Chikazu Daichi , Tomihara Kei , Mishima Katsuaki , Otsuru Mitsunobu , Asoda Seiji , Fujiwara Shigeyoshi , Ohyama Yoshio , Kurita Hiroshi , Kawamata Hitoshi , Fukuda Masayuki , Shintani Yukari , Kobayashi Takanori , Kanno Takahiro , Oh‐iwa Ichiro , Kawano Kenji , Yamashita Yoshio , Kobayashi Wataru , Ohiro Yoichi , Uzawa Katsuhiro , Ota Yoshihide , Kirita Tadaaki
Published: December 2022

Objectives

Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients.

Materials and Methods

This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression‐free and overall survival. Progression‐free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression‐free and overall survival were identified using multivariate analysis.

Results

Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1‐ and 2‐year progression‐free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression‐free survival were performance status and immune‐related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune‐related adverse events.

Conclusion

Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.
Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy
Authors: Xie Lu , Chen Chenglong , Liang Xin , Xu Jie , Sun Xin , Sun Kunkun , Yang Rongli , Tang Xiaodong , Guo Wei
Published: December 2022

Objectives

The fact that studies on anti‐programmed cell death 1 (PD‐1) or its relevant ligand 1 (PD‐L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various checkpoint molecules with immunohistochemistry in osteosarcoma specimens and analyzed the relationship of the expression of these checkpoint molecules with patients' clinical courses.

Methods

This study was a retrospective non‐intervention study from August 1st 2017 to March 1st 2020. Immunohistochemistry for B7‐H3 (CD276, Cluster of Differentiation 276), CD47 (Cluster of Differentiation 47), PD‐L1 (programmed cell death ligand 1), TIM3 (mucin‐domain containing‐3), TGF‐β (TransformingGrowth Factor β), CXCR 4 (Chemokine Receptor 4), CD27 (Cluster of Differentiation 27), IDO1 (Indoleamine 2,3‐dioxygenase 1), KIRs (Killer cell Immunoglobulin‐like Receptors), and SDF‐1 (Stromal cell‐Derived Factor‐1) was performed on 35 resected osteosarcoma specimens. Patients progressed upon first‐line chemotherapy with evaluable lesions were qualified for this study, and their specimens previously stored in the pathological department repository would be retrieved for analysis. Associations between the immunohischemistry markers and clinicopathological variables and survival were evaluated by the χ2 displayed by cross‐table, Cox proportional hazards regression model, and Kaplan–Meier plots.

Results

The positive rates of B7‐H3, CD47, PD‐L1, TIM3, and TGF‐β expression in this sample of 35 heavily treated osteosarcomas were 29% (10/35), 15% (5/35), 9% (3/35), 6% (2/35), and 6% (2/35), respectively, and diverse staining intensities were observed. Among these advanced patients, 15/35 (43%) had positive checkpoint expression, of which 33% (5/15) showed evidence of the co‐expression of more than one checkpoint molecule. We did not find any obvious correlation with clinicopathological characteristics and the positive expression of these molecules.

Conclusions

The present study highlights that only a small subset of progressive osteosarcomas, which had been heavily‐treated, expressed tumor immune‐associated checkpoint molecules, of which B7‐H3 was the most positively expressed checkpoint and might be a promising target for further osteosarcoma investigation.
Potato protein tyrosine phosphatase StPTP1a is activated by StMKK1 to negatively regulate plant immunity
Authors: Li Fangfang , Chen Xiaokang , Yang Ruixin , Zhang Kun , Shan Weixing , Joosten Matthieu H. A. J. , Du Yu
Published: December 2022

Phytophthora infestans causes severe losses in potato production. The MAPK kinase StMKK1 was previously found to negatively regulate potato immunity to P. infestans. Our results showed that StMKK1 interacts with a protein tyrosine phosphatase, referred to as StPTP1a, and StMKK1 directly phosphorylates StPTP1a at residues Ser‐99, Tyr‐223 and Thr‐290. StPTP1a is a functional phosphatase and the phosphorylation of StPTP1a at these three residues enhances its stability and catalytic activity. StPTP1a negatively regulates potato immunity and represses SA‐related gene expression. Furthermore, StPTP1a interacts with, and dephosphorylates, the StMKK1 downstream signalling targets StMPK4 and −7 at their Tyr‐203 residue resulting in the repression of salicylic acid (SA)‐related immunity. Silencing of NbPTP1a + NbMPK4 or NbPTP1a + NbMPK7 abolished the plant immunity to P. infestans caused by NbPTP1a silencing, indicating that PTP1a functions upstream of NbMPK4 and NbMPK7. StMKK1 requires StPTP1a to negatively regulate SA‐related immunity and StPTP1a is phosphorylated and stabilized during immune activation to promote the de‐phosphorylation of StMPK4 and −7. Our results reveal that potato StMKK1 activates and stabilizes the tyrosine phosphatase StPTP1a that in its turn de‐phosphorylates StMPK4 and −7, thereby repressing plant SA‐related immunity.
Delusions of parasitosis and delusions of parasitosis by proxy in a mother and her children
Authors: Kalra Kisha , Whittington Carli P. , Sevey Whitney , Hunt Elizabeth , Metz James B.
Published: December 2022

Delusions of parasitosis by proxy is an uncommon entity wherein an individual projects a delusional belief onto another person who lacks capacity to hold the same belief. We report a case of delusions of parasitosis by proxy in a mother who believed that she was infested with scabies and projected her fixed, delusional belief of scabies infestation onto her children. She subjected her children to numerous home remedies and medical treatments as well as removing them from school in an effort to cure them of the supposed infestation. Child maltreatment can be a concern in such cases with a low threshold for involving child protective services if harm to the children is suspected.
Utilization of SARS‐CoV‐2‐Positive donors in pediatric renal transplantation
Authors: Pizzo Helen , Soni Priya R. , Nadipuram Santhosh , Garrison Jonathan , Jordan Stanley C. , Puliyanda Dechu
Published: December 2022

Background

As COVID‐19‐positive donors are becoming more common, there is an increasing need for the transplant community to evaluate the safety and efficacy of organ transplant from a SARS‐CoV‐2‐infected donor.

Methods

Here we describe outcomes of two pediatric kidney transplant recipients who were vaccinated against COVID‐19 and received their allograft from a SARS‐CoV‐2‐positive donor.

Results

Both donors did not die from a COVID‐19‐related illness; the first donor had 1 week of COVID‐19 symptoms 4 weeks prior to donation and the second was asymptomatic. Donor 1 had a Ct of 33.4 at 3 days and Donor 2 with a Ct of 37.2 at 16 days prior to donation. The first recipient was positive for SARS‐CoV‐2 anti‐spike IgG on the day of transplant, but the second patient was negative and both patients received IVIg perioperatively. There was no evidence of SARS‐CoV‐2 transmission or compromised renal function at 86‐ and 80‐day post‐transplant, respectively.

Conclusions

This case series suggests favorable short‐term outcomes with accepting SARS‐CoV‐2‐positive donors for pediatric renal transplantation, after thorough evaluation of the donor's risk for transmission, assessing the recipient's serologic status to SARS‐CoV‐2, and considering pre‐emptive measures to mitigate the risk for severe COVID‐19 should the recipient acquire donor‐derived SARS‐CoV‐2.
Potential distribution of the citrus Mal Secco disease in the Mediterranean basin under current and future climate conditions
Authors: Krasnov Helena , Ezra David , Bahri Bochra A. , Cacciola Santa O. , Meparishvili Galina , Migheli Quirico , Blank Lior
Published: December 2022

Species distribution models are widely used to estimate the potential geographic distribution of species habitat. They are also used to predict the impact of climate change on species distributions. In this study, we examined the distribution of Mal Secco disease, an infective disease of citrus caused by the fungus Plenodomus tracheiphilus. To model the Mal Secco distribution under current and two future (2050 and 2070) climatic scenarios in the Mediterranean basin, eight climate variables were incorporated into the Maximum Entropy (MaxEnt) model. All three model distributions had high AUC values (0.97), indicating excellent performance. The precipitation during the wettest month and the minimum temperature during the coldest month contributed the most to the model. The suitable areas for the Mal Secco disease were predicted to decrease by up to 23% by the year 2070. For each of the three scenarios, the change in the proportion of suitable areas along the longitudinal (west–east) and latitudinal (south–north) geographical axes of the Mediterranean basin showed a similar trend. Our study highlights the supposition that while climate change is likely to reduce the extent of suitable areas, no range shift is expected to occur in the Mediterranean basin.
Relationship between the fear of COVID‐19 and social isolation and depression in elderly individuals
Authors: Kilic Dilek , Aslan Gülpınar , Ata Gülnaz , Bakan Ayse B. Savci
Published: December 2022

Background

The COVID‐19 pandemic has seriously affected elderly individuals and it has been associated with high morbidity and mortality rates. This study was conducted to examine the relationship between fear of COVID‐19, social isolation and depression in elderly individuals.

Methods

The study is a descriptive type. The sample consisted of 362 elderly people. The study data were collected using the Introductory Information Form, the Fear of COVID‐19 Scale, the Nottingham Health Profile Social Isolation Scale and the Geriatric Depression Scale‐Short Form.

Results

It was determined there was a positive and moderate relationship between fear of COVID‐19 and depression and social isolation, and a positive and high relationship between social isolation and depression, and the results were statistically significant (P < 0.001).

Conclusions

Public health nurses, during epidemic periods, should help elderly individuals manage their fears about the disease. In addition, they should lead the practices that can sustain social participation and prevent depression in the elderly.