bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species-specific partial gene duplication in Arabidopsis thaliana evolved novel phenotypic effects on morphological traits under strong positive selection
Authors: Huang Yuan , Chen Jiahui , Dong Chuan , Sosa Dylan , Xia Shengqian , Ouyang Yidan , Fan Chuanzhu , Li Dezhu , Mortola Emily , Long Manyuan , Bergelson Joy 
Published: December 2021

Abstract
Gene duplication is increasingly recognized as an important mechanism for the origination of new genes, as revealed by comparative genomic analysis. However, how new duplicate genes contribute to phenotypic evolution remains largely unknown, especially in plants. Here, we identified the new gene EXOV, derived from a partial gene duplication of its parental gene EXOVL in Arabidopsis thaliana. EXOV is a species-specific gene that originated within the last 3.5 million years and shows strong signals of positive selection. Unexpectedly, RNA-sequencing analyses revealed that, despite its young age, EXOV has acquired many novel direct and indirect interactions in which the parental gene does not engage. This observation is consistent with the high, selection-driven substitution rate of its encoded protein, in contrast to the slowly evolving EXOVL, suggesting an important role for EXOV in phenotypic evolution. We observed significant differentiation of morphological changes for all phenotypes assessed in genome-edited and T-DNA insertional single mutants and in double T-DNA insertion mutants in EXOV and EXOVL. We discovered a substantial divergence of phenotypic effects by principal component analyses, suggesting neofunctionalization of the new gene. These results reveal a young gene that plays critical roles in biological processes that underlie morphological evolution in A. thaliana.
Distinct neuroanatomic subtypes in antipsychotic-treated patients with schizophrenia classified by the predefined classification in a never-treated sample
Authors: Zhao Qiannan , Li Jiao , Xiao Yuan , Cao Hengyi , Wang Xiao , Zhang Wenjing , Li Siyi , Liao Wei , Gong Qiyong , Lui Su 
Published: December 2021

Abstract

Background
Distinct neuroanatomic subtypes have been identified in never-treated patients with schizophrenia based on cerebral structural abnormalities, but whether antipsychotic-treated patients would be stratified under the guidance of such previously formed classification remains unclear.

Objective
The present study aimed to investigate alterations of brain structures in antipsychotic-treated patients with schizophrenia based on a predefined morphological classification and their relationships with cognitive performance.

Methods
Cortical thickness, surface area, and subcortical volume were extracted from 147 antipsychotic-treated patients with schizophrenia using structural magnetic resonance imaging for classification. The Brief Assessment of Cognition in Schizophrenia (BACS) and Positive and Negative Syndrome Scale (PANSS) were used to assess cognition and symptoms.

Results
Antipsychotic-treated patients were categorized into three subtypes with distinct patterns of brain morphological alterations. Subtypes 1 and 2 were characterized by widespread deficits in cortical thickness but relatively limited deficits in surface area. In contrast, subtype 3 demonstrated cortical thickening mainly in parietal-occipital regions and widespread deficits in surface area. All three subgroups demonstrated cognitive deficits compared with healthy controls. Significant associations between neuroanatomic and cognitive abnormalities were only observed in subtype 1, where cortical thinning in the left lingual gyrus was conversely related to symbol coding performance.

Conclusions
Similar to drug-naïve patients, neuroanatomic heterogeneity exists in antipsychotic-treated patients, with disparate associations with cognition. These findings promote our understanding of relationships between neuroanatomic abnormalities and cognitive performance in the context of heterogeneity. Moreover, these results suggest that neurobiological heterogeneity needs to be considered in cognitive research in schizophrenia.
Correlation between salivary gland ultrasonography and scintigraphy in primary Sjögren’s syndrome
Authors: Min Hong Ki , Kim Se Hee , Lee Kyung-Ann , Jo Joon-Hyung , So Young , Chung Hyun Woo , Lee Sang-Heon , Kim Hae-Rim 
Published: December 2021

Abstract

Objective
To compare findings on salivary gland ultrasonography (SGUS) and salivary gland scintigraphy (SGS) in patients with primary SS (pSS).

Methods
The study cohort included patients newly diagnosed with pSS who underwent SGUS and SGS at the same time at our tertiary care hospital. Baseline demographics, laboratory data, clinical data and SGUS and SGS findings were collected. An SGUS cut-off score ≥14 defined positive SGUS findings and was used to classify patients in SGUS+ and SGUS− groups. SGS findings were quantified by the parotid:submandibular uptake ratio (PU:SU) and percentage parotid/submandibular excretion (%PE/%SE). The correlation between SGUS and SGS findings was evaluated.

Results
For analysis, 18 patients with SGUS+ findings and 18 with SGUS− findings were recruited, for a total study cohort of 36 patients. There were no between-group differences in baseline demographics and clinical and laboratory data. The PU, %PE, SU and %SE were significantly lower in the SGUS+vs SGUS− group. The SGUS score for the parotid gland was negatively correlated to the PU (r = −0.36, P = 0.03) and %PE (r = −0.35, P = 0.04). The SGUS score of the submandibular gland was negatively correlated to the SU (r = −0.42, P = 0.01) and %SE (r = −0.39, P = 0.02).

Conclusions
Patients with a higher SGUS score had lower salivary gland function. The SGUS score showed a significant correlation with PU, %PE, SU and %SE. These findings are indicative of a possible predictive role of SGUS to diagnose salivary gland dysfunction.
Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
Authors: Dahlqvist Johanna , Ekman Diana , Sennblad Bengt , Kozyrev Sergey V , Nordin Jessika , Karlsson Åsa , Meadows Jennifer R S , Hellbacher Erik , Rantapää-Dahlqvist Solbritt , Berglin Ewa , Stegmayr Bernd , Baslund Bo , Palm Øyvind , Haukeland Hilde , Gunnarsson Iva , Bruchfeld Annette , Segelmark Mårten , Ohlsson Sophie , Mohammad Aladdin J , Svärd Anna , Pullerits Rille , Herlitz Hans , Söderbergh Annika , Rosengren Pielberg Gerli , Hultin Rosenberg Lina , Bianchi Matteo , Murén Eva , Omdal Roald , Jonsson Roland , Eloranta Maija-Leena , Rönnblom Lars , Söderkvist Peter , Knight Ann , Eriksson Per , Lindblad-Toh Kerstin 
Published: December 2021

Abstract

Objective
To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV).

Methods
Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay.

Results
PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10−61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10−44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10−10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10−25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10−7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele.

Conclusion
We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
Search-Based Peer Groups and Commonality in Liquidity
Authors: Brockman Paul , Chung Dennis Y , Snow Neal M 
Published: December 2021

Abstract
We examine search-based peer (SBP) groups proposed by Lee, Ma, and Wang (2015) and their relationship with commonality in liquidity. Our results confirm that SBP affiliation is a significant determinant of commonality in liquidity and, unlike market- and industry-commonality, SBP-commonality has been increasing over the past 15 years. We separate retail from institutional investor queries by tracing the IP locations of Electronic Data Gathering, Analysis, and Retrieval (EDGAR) searches. Our results show that retail investors are responsible for roughly 85% of the EDGAR searches that generate SBP groups. Overall, our study provides new evidence of a significant demand-side commonality associated with SBP affiliations.
Longitudinal Comparison of Continuing Medical Education Learning Objectives and Intent-to-Change Statements of Participants
Authors: Dunson Blake , Park Yoon Soo , Richards Boyd , Hirshfield Laura E. , Jensen Randy L. 
Published: December 2021

Introduction:
Successful completion of continuing medical education (CME) activities is often required for ongoing physician board certification, licensure, and hospital privileges. CME activities are designed to address professional knowledge or practice gaps. The authors examined participants' “intent to change” after CME activities to evaluate whether CME activity content was suitably linked with the stated learning objectives.

Methods:
The authors performed a retrospective mixed-methods thematic content analysis of written and electronic records from American Association of Neurological Surgeons–sponsored CME activities. Data from 2011 through 2016 were analyzed using a quantitative, deductive content analysis approach. Data were examined for each year separately as well as longitudinally over the six consecutive years. Intent-to-change data that did not align with meeting objectives were analyzed inductively using a qualitative content analysis approach to explore potential unintended learning themes.

Results:
The authors examined 85 American Association of Neurological Surgeons CME activities (424 CME objectives). The objectives were compared with 1950 intent-to-change statements. Thematic patterns of recurrent intent-to-change statements that matched with CME objectives included topics of resident education, complication avoidance, clinical best practices and evidence, new innovations, and novel surgical techniques. Just over a third of intent-to-change statements (37.3%) were not related to any meeting objective. Approximately a quarter of these unmatched statements led to new learning objectives in subsequent years.

Conclusions:
An examination of CME learning objectives and participant intent-to-change statements provides information for examination of both meeting planner and learner attitudes for future CME activity planning.
Effectiveness and Dissemination of the Interprofessional Pediatric Pain PRN Curriculum
Authors: Manworren Renee C. B. , Basco Megan 
Published: December 2021

Introduction:
Cultural transformation is needed for health care to be sensitive to children's pain. The Pediatric Pain Practice Registered Nurses (PRN) Curriculum is the first free, open access, downloadable, interprofessional pain continuing education (IPPCE) curriculum developed to empower health care professionals to translate evidence-based pain care into clinical practice. To evaluate the curriculum and its experiential flipped-learning strategies, we used a mixed methods approach.

Methods:
Interprofessional pediatric teams from eight health care systems evaluated the curriculum after attending Pediatric Pain PRN Courses in the Fall of 2017 (N = 90). Qualitative methods were used to evaluate the acceptability, feasibility, and utility of the curriculum and IPPCE strategies. Pain knowledge and attitudes were measured pre-IPPCE/post-IPPCE with the Pediatric Healthcare Provider's Knowledge & Attitude Survey Regarding Pain (PHPKAS). Web analytics were used to describe dissemination for the first year after the curriculum's webpage launch.

Results:
Learners rated their achievement of course objectives as moderate–great. PHPKAS scores significantly increased (P < .0005); but significant differences in physician and nurse PHPKAS question responses pre-IPPCE/post-IPPCE were found. Within 2 years of the IPPCE, three health care systems were certified as Childkind Hospitals, five Pediatric Pain PRN Programs were established, and various practice changes and improved patient outcomes, such as decreased hospital lengths of stay and emergency department returns for pain, were realized. Curriculum dissemination was global.

Discussion:
Results support the acceptability, effectiveness, feasibility, utility, and global dissemination of the curriculum and IPPCE strategies. More rigorous patient outcome data are needed; however, this study demonstrated the benefit of a free, open-access, downloadable, interprofessional health care provider continuing education curriculum.
Rho kinase inhibition ameliorates vascular remodeling and blood pressure elevations in a rat model of apatinib-induced hypertension
Authors: Li Caie , Ma Liping , Wang Qiongying , Shao Xuejiao , Guo Lu , Chen Jianshu , Wang Wenjuan , Yu Jing 
Published: December 2021

Objectives:
Hypertension is one of the major adverse effects of tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors. However, the mechanism underlying TKIs-induced hypertension remains unclear. Here, we explored the role of the RhoA/Rho kinase (ROCK) signaling pathway in elevation of blood pressure (BP) induced by apatinib, a selective TKI approved in China for treatment of advanced or metastatic gastric cancer. A nonspecific ROCK inhibitor, Y27632, was then combined with apatinib and its efficacy in alleviating apatinib-induced hypertension was evaluated.

Methods:
Normotensive female Wistar–Kyoto rats were exposed to two different doses of apatinib, or apatinib combined with Y27632, or vehicle for 2 weeks. BP was monitored by a tail-cuff plethysmography system. The mRNA levels and protein expression in the RhoA/ROCK pathway were determined, and vascular remodeling assessed.

Results:
Administration of either a high or low dose of apatinib was associated with a rapid rise in BP, reaching a plateau after 12 days. Apatinib treatment mediated upregulation of RhoA and ROCK II in the mid-aorta, more significant in the high-dose group. However, ROCK I expression showed no statistically significant differences. Furthermore, the mRNA level of GRAF3 decreased dose-dependently. Apatinib administration was also associated with decreased levels of MLCP, and elevated endothelin-1 (ET-1) and collagen I, which were accompanied with increased mid-aortic media. However, treatment with Y27632 attenuated the above changes.

Conclusion:
These findings suggest that activation of the RhoA/ROCK signaling pathway could be the underlying mechanism of apatinib-induced hypertension, while ROCK inhibitor have potential therapeutic value.
Rapid Viral Testing and Antibiotic Prescription in Febrile Children With Respiratory Symptoms Visiting Emergency Departments in Europe
Authors: Tan Chantal D. , Hagedoorn Nienke N. , Dewez Juan E. , Borensztajn Dorine M. , von Both Ulrich , Carrol Enitan D. , Emonts Marieke , van der Flier Michiel , de Groot Ronald , Herberg Jethro , Kohlmaier Benno , Levin Michael , Lim Emma , Maconochie Ian K. , Martinon-Torres Federico , Nijman Ruud G. , Pokorn Marko , Rivero-Calle Irene , Strle Franc , Tsolia Maria , Vermont Clementien L. , Yeung Shunmay , Zachariasse Joany M. , Zenz Werner , Zavadska Dace , Moll Henriette A. 
Published: December 2021

Background.
Inappropriate antibiotic prescribing often occurs in children with self-limiting respiratory tract infections, contributing to antimicrobial resistance. It has been suggested that rapid viral testing can reduce inappropriate antibiotic prescribing. We aimed to assess the association between rapid viral testing at the Emergency Department (ED) and antibiotic prescription in febrile children.

Methods.
This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0–18 years) attending 12 European EDs. In children with respiratory symptoms visiting 6 EDs equipped with rapid viral testing, we performed multivariable logistic regression analysis regarding rapid viral testing and antibiotic prescription adjusted for patient characteristics, disease severity, diagnostic tests, focus of infection, admission, and ED.

Results.
A rapid viral test was performed in 1061 children (8%) and not performed in 11,463 children. Rapid viral test usage was not associated with antibiotic prescription (aOR 0.9, 95% CI: 0.8–1.1). A positive rapid viral test was associated with less antibiotic prescription compared with children without test performed (aOR 0.6, 95% CI: 0.5–0.8), which remained significant after adjustment for CRP and chest radiograph result. Twenty percent of the positively tested children received antibiotics. A negative rapid viral test was not associated with antibiotic prescription (aOR 1.2, 95% CI: 1.0–1.4).

Conclusions.
Rapid viral test usage did not reduce overall antibiotic prescription, whereas a positive rapid viral test did reduce antibiotic prescription at the ED. Implementation of rapid viral testing in routine emergency care and compliance to the rapid viral test outcome will reduce inappropriate antibiotic prescribing at the ED.
Re-examining Hepatitis B Postexposure Prophylaxis Following Pediatric Community-acquired Needle-stick Injury in an Era of a National Immunization Registry
Authors: Ewe Krist Y.H. , Blyth Christopher C. , McLeod Charlie , Borland Meredith L. , Bowen Asha C. , Yeoh Daniel K. , Campbell Anita J. 
Published: December 2021

Background:
Long-term hepatitis B immunity has been demonstrated following the completion of the primary vaccination series in childhood. Some guidelines recommend a hepatitis B surface antibody (anti-HBs) directed approach following community-acquired needle-stick injury (CANSI) to inform hepatitis B postexposure prophylaxis (PEP) management. We assessed the utility of anti-HBs testing post-CANSI, as well as the costing of, and adherence to PEP at a pediatric hospital.

Methods:
Children presenting to an Australian tertiary pediatric hospital post-CANSI (2014–2019) were identified retrospectively using medical and laboratory records. Immunization status was obtained from the Australian Immunisation Registry.

Results:
Fifty-six children with CANSI were identified. Of those with immunization records, all had completed hepatitis B vaccinations (n = 52). At presentation, 44% (n = 23) had anti-HBs <10 IU/L, which was more likely in older (≥6 years, 68%) versus younger children (OR 4.59, P < 0.02). HBIG and hepatitis B vaccine adherence was 65% (15/23) and 78% (18/23), respectively. All children (n = 14) with anti-HBs ≥4 weeks postvaccination ±HBIG, demonstrated an anamnestic response. No hepatitis B infections were detected. Using completed immunizations versus anti-HBs levels as a marker of immunity to direct PEP resulted in a projected cost savings of AUD$ 4234.

Conclusion:
Anti-HBs levels <10 IU/L, despite previous vaccinations, were frequent in children post-CANSI, with many demonstrating an anamnestic response. Adherence to postexposure HBIG and hepatitis B vaccine was suboptimal using an anti-HBs directed approach. These data support re-evaluating PEP in an era of the national immunization registry; completion of hepatitis B vaccinations as a marker of immunity provides a practical approach, ensuring optimized care for pediatric CANSI.
Pediatric Parapneumonic Effusion/Pleural Empyema in Japan
Authors: Hoshino Tadashi , Nishima Daisuke , Enseki Mayumi , Umehara Naoki , Fukasawa Chie , Ishiwada Naruhiko 
Published: December 2021

Background:
Pediatric parapneumonic effusion/ pleural empyema (PPE/PE) is a severe infectious condition, and its management should be guided by local epidemiology and the patient’s medical history. This survey aimed to determine the clinical and bacteriologic features of PPE/PE in Japan.

Methods:
A nationwide retrospective questionnaire survey was conducted, targeting 159 pediatric specialist training medical facilities for inpatients ≤18 years of age who were admitted for PPE/PE between January 2007 and December 2016.

Results:
Valid responses were obtained from 122 facilities, and 96 patients were identified from 38 facilities. The median age (interquartile range) was 2.7 (0.8–7.8) years. Overall, 60 (63 %) patients were men and 49 (51%) had comorbidities. The causative bacteria were identified in 59% of patients by culture except in one case identified using PCR. Streptococcus pyogenes (16%), Staphylococcus aureus (14%) and Streptococcus pneumoniae (13%) were the major pathogens. Carbapenems were administered to 34% of patients without comorbidities. Chest tube drainage was performed in 71%, intrapleural fibrinolytic therapy in 9.4%, surgery in 25% and mechanical ventilation in 29% of the patients. Five patients (5.2%) had complications and one (1.1%) had sequelae, but all patients (100%) survived.

Conclusions:
This is first report of a nationwide survey pertaining to pediatric PPE/PE in Japan. We found that the etiology showed a different trend from that reported in other countries. It is worrisome that molecular methods were rarely used for pathogenic diagnosis and carbapenems were overused. Thus, it is imperative to establish clinical guidelines for PPE/PE in Japan.
Differential Impact of Nonpharmaceutical Interventions on the Epidemiology of Invasive Bacterial Infections in Children During the Coronavirus Disease 2019 Pandemic
Authors: Kim Ye Kyung , Choi Youn Young , Lee Hyunju , Song Eun Song , Ahn Jong Gyun , Park Su Eun , Lee Taekjin , Cho Hye-Kyung , Lee Jina , Kim Yae-Jean , Jo Dae Sun , Kang Hyun Mi , Lee Joon Kee , Kim Chun Soo , Kim Dong Hyun , Kim Hwang Min , Choi Jae Hong , Eun Byung Wook , Kim Nam Hee , Cho Eun Young , Kim Yun-Kyung , Oh Chi Eun , Kim Kyung-Hyo , Choi Eun Hwa 
Published: December 2021

Background:
Invasive bacterial infection (IBI) remains a major burden of mortality and morbidity in children. As coronavirus disease 2019 (COVID-19) emerged, stringent nonpharmaceutical interventions (NPIs) were applied worldwide. This study aimed to evaluate the impact of NPIs on pediatric IBI in Korea.

Methods:
From January 2018 to December 2020, surveillance for pediatric IBIs caused by 9 pathogens (S. pneumoniae, H. influenzae, N. meningitidis, S. agalactiae, S. pyogenes, S. aureus, Salmonella species, L. monocytogenes and E. coli) was performed at 22 hospitals throughout Korea. Annual incidence rates were compared before and after the COVID-19 pandemic.

Results:
A total of 651 cases were identified and the annual incidence was 194.0 cases per 100,000 in-patients in 2018, 170.0 in 2019 and 172.4 in 2020. Most common pathogen by age group was S. agalactiae in infants < 3 months (n = 129, 46.7%), S. aureus in 3 to < 24 months (n = 35, 37.2%), Salmonella spp. in 24 to < 60 months (n = 24, 34.8%) and S. aureus in children ≥ 5 years (n = 128, 60.7%). Compared with 2018 to 2019, the incidence rate in 2020 decreased by 57% for invasive pneumococcal disease (26.6 vs. 11.5 per 100,000 in-patients, P = 0.014) and 59% for Salmonella spp. infection (22.8 vs. 9.4 per 100,000 in-patients, P = 0.018). In contrast, no significant changes were observed in invasive infections due to S. aureus, S. agalactiae and E. coli.

Conclusions:
The NPIs implemented during the COVID-19 pandemic reduced invasive diseases caused by S. pneumoniae and Salmonella spp. but not S. aureus, S. agalactiae and E. coli in children.