bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymoma
Authors: de Almeida Magalhães Taciani , Alencastro Veiga Cruzeiro Gustavo , Ribeiro de Sousa Graziella , Englinger Bernhard , Fernando Peinado Nagano Luis , Ancliffe Mathew , Rodrigues da Silva Keteryne , Jiang Li , Gojo Johannes , Cherry Liu Yulu , Carline Brooke , Kuchibhotla Mani , Pinto Saggioro Fabiano , Kazue Nagahashi Marie Suely , Mieko Oba-Shinjo Sueli , Andres Yunes José , Gomes de Paula Queiroz Rosane , Alberto Scrideli Carlos , Endersby Raelene , Filbin Mariella G , Silva Borges Kleiton , Salic Adrian , Gonzaga Tone Luiz , Valera Elvis Terci 
Published: June 2022

Abstract

Background
Supratentorial RELA fusion (ST-RELA) ependymomas (EPNs) are resistant tumors without an approved chemotherapeutic treatment. Unfortunately, the molecular mechanisms that lead to chemoresistance traits of ST-RELA remain elusive. The aim of this study was to assess RELA fusion-dependent signaling modules, specifically the role of the Hedgehog (Hh) pathway as a novel targetable vulnerability in ST-RELA.

Methods
Gene expression was analyzed in EPN from patient cohorts, by microarray, RNA-seq, qRT-PCR, and scRNA-seq. Inhibitors against Smoothened (SMO) (Sonidegib) and Aurora kinase A (AURKA) (Alisertib) were evaluated. Protein expression, primary cilia formation, and drug effects were assessed by immunoblot, immunofluorescence, and immunohistochemistry.

Results
Hh components were selectively overexpressed in EPNs induced by the RELA fusion. Single-cell analysis showed that the Hh signature was primarily confined to undifferentiated, stem-like cell subpopulations. Sonidegib exhibited potent growth-inhibitory effects on ST-RELA cells, suggesting a key role in active Hh signaling; importantly, the effect of Sonidegib was reversed by primary cilia loss. We, thus, tested the effect of AURKA inhibition by Alisertib, to induce cilia stabilization/reassembly. Strikingly, Alisertib rescued ciliogenesis and synergized with Sonidegib in killing ST-RELA cells. Using a xenograft model, we show that cilia loss is a mechanism for acquiring resistance to the inhibitory effect of Sonidegib. However, Alisertib fails to rescue cilia and highlights the need for other strategies to promote cilia reassembly, for treating ST-RELA tumors.

Conclusion
Our study reveals a crucial role for the Hh pathway in ST-RELA tumor growth, and suggests that rescue of primary cilia represents a vulnerability of the ST-RELA EPNs.
Acceptance of skin products in healthcare workers: an empirical investigation
Authors: Symanzik C , Skudlik C , John S M 
Published: June 2022

Abstract

Background
Healthcare workers (HCWs) are at high risk of developing hand eczema (HE). This can be exacerbated by hygiene measures related to the coronavirus disease (COVID-19). Using mild skin cleansers and emollients or moisturizers is central in the prevention of HE—especially with increased COVID-19 hygiene regimes.

Aims
This study aimed to assess parameters important for the acceptance of a skincare concept in HCWs.

Methods
In this proof-of-concept user trial, HCWs were provided ad libitum with hand wash oil and hand cream during the 6-month period, when occupationally acquired COVID-19 infections among HCWs were peaking in Germany and then surveyed about acceptance of the products using questionnaires.

Results
Of 135 HCWs, 115 (85%) responded. Skin tolerance of the hand wash oil and the hand cream was rated very good by 63% and 52% of the 115 participants, respectively. Of the 115 participants, 58% and 57% were very satisfied with the hand wash oil and the hand cream, respectively.

Conclusions
Acceptance of skin cleansing and skincare products in HCWs seems influenced by parameters such as self-assessed skin tolerance and self-reported overall satisfaction. It must be assumed that products are only used as recommended if they are well-accepted. Employers might survey employees about acceptance of products using the parameters identified to adjust concepts if necessary to sustainably contribute to the prevention of HE.
Experimentally reduced feather microbial loads improve reproductive performance in captive Zebra Finches
Authors: Burley Nancy Tyler , Azevedo Campos Felipe , Chien Emilie , Duarte Shauna , Kirshman Nathalie , Phan Alison Thuy Tien N , Wilson Kerianne M 
Published: June 2022

AbstractWe performed a laboratory experiment on caged, domesticated Australian Zebra Finches (Taeniopygia guttata castanotis) to assess the effects of antimicrobial treatment applied to birds’ plumage on the feather microbial loads of breeding pairs and their associated reproductive performance. Treatments included an experimental group that experienced frequent misting with a broad-spectrum antimicrobial, as well as 2 control groups. Microbial loads (colony forming units [CFUs]) sampled from the belly feathers of breeders were higher posthatching than prehatching, and experimental pairs had lower loads (one-half to one-third the CFU counts) than controls at all sampled breeding-cycle stages. Clutch size and hatching success did not differ among treatments, but experimental pairs fledged nearly 50% more offspring (mean = 3.5 per clutch) than controls (mean = 2.3 per clutch) due to experiencing much lower nestling mortality. Offspring development rate, as assessed by one metric, varied among treatments: beak color score sampled midway in the development of adult phenotype revealed that offspring of experimental pairs had more rapid development. Findings imply that experimentally reduced density of feather microbial loads on breeders decreased reproductive costs in the posthatch phase, resulting in increased offspring survival and condition. At the time offspring fledged, uropygial gland volume tended to be greater among breeders that had experienced antimicrobial application throughout the breeding cycle. These results are consistent with a growing literature showing that the feather microbiome contributes significantly to the evolution of avian life histories and behavior and indicate that Zebra Finches are a useful laboratory model for investigating in vivo effects of the feather microbiome on avian hosts.
Time to act: Early experience suggests stabilization care offers a feasible approach for adolescents after acute life-threatening opioid toxicity
Authors: Moore Eva M , Warshawski Tom , Jassemi Sara , Charles Grant , Vo Dzung X 
Published: June 2022

Abstract
British Columbia is the epicentre of the opioid crisis in North America. Illicit drug toxicity is now one of the top 3 causes of death for adolescents in British Columbia. Evidence informed treatment is available but adolescents rarely receive it. Non-fatal toxicity can provide an opportunity to intervene. Since 2018, paediatricians in British Columbia have been offering admission, involuntary if necessary, to adolescents presenting to hospital after a life-threatening illicit drug toxicity. This brief stay, termed “stabilization care,” offers medical and psychiatric assessments, withdrawal management and initiation of opioid agonist therapy and discharge planning. Hospital policies, procedures and protocols were revised to support the unique needs of this population. Early experience with 17 adolescents shows relatively high attachment to treatment services and opioid agonist treatment, suggesting that paediatric interdisciplinary teams, working strategically, can improve care for adolescents in the face of the opioid epidemic.
Phosphorylation of OsTGA5 by casein kinase II compromises its suppression of defense-related gene transcription in rice
Authors: Niu Yuqing , Huang Xiaoguang , He Zexue , Zhang Qingqing , Meng Han , Shi Hua , Feng Baomin , Zhou Yuanchang , Zhang Jianfu , Lu Guodong , Wang Zonghua , Zhang Wenli , Tang Dingzhong , Wang Mo 
Published: June 2022

AbstractPlants manage the high cost of immunity activation by suppressing the expression of defense genes during normal growth and rapidly switching them on upon pathogen invasion. TGAs are key transcription factors controlling the expression of defense genes. However, how TGAs function, especially in monocot plants like rice with continuously high levels of endogenous salicylic acid (SA) remains elusive. In this study, we characterized the role of OsTGA5 as a negative regulator of rice resistance against blast fungus by transcriptionally repressing the expression of various defense-related genes. Moreover, OsTGA5 repressed PTI responses and the accumulation of endogenous SA. Importantly, we showed that the nucleus-localized casein kinase II (CK2) complex interacts with and phosphorylates OsTGA5 on Ser-32, which reduces the affinity of OsTGA5 for the JIOsPR10 promoter, thereby alleviating the repression of JIOsPR10 transcription and increasing rice resistance. Furthermore, the in vivo phosphorylation of OsTGA5 Ser-32 was enhanced by blast fungus infection. The CK2 α subunit, depending on its kinase activity, positively regulated rice defense against blast fungus. Taken together, our results provide a mechanism for the role of OsTGA5 in negatively regulating the transcription of defense-related genes in rice and the repressive switch imposed by nuclear CK2-mediated phosphorylation during blast fungus invasion.
Revisiting the origin and identity specification of the spikelet: A structural innovation in grasses (Poaceae)
Authors: Wang Yanli , Bi Xiaojing , Zhong Jinshun 
Published: June 2022

AbstractSpikelets are highly specialized and short-lived branches and function as a constitutional unit of the complex grass inflorescences. A series of genetic, genomic, and developmental studies across different clades of the family have called for and permitted a synthesis on the regulation and evolution of spikelets, and hence inflorescence diversity. Here, we have revisited the identity specification of a spikelet, focusing on the diagnostic features of a spikelet from morphological, developmental, and molecular perspectives. Particularly, recent studies on a collection of barley (Hordeum vulgare L.), wheat (Triticum spp.), and rice (Oryza sativa L.) mutants have highlighted a set of transcription factors that are important in the control of spikelet identity and the patterning of floral parts of a spikelet. In addition, we have endeavored to clarify some puzzling issues on the (in)determinacy and modifications of spikelets over the course of evolution. Meanwhile, genomes of two sister taxa of the remaining grass species have again demonstrated the importance of genome duplication and subsequent gene losses on the evolution of spikelets. Accordingly, we argue that changes in the orthologs of spikelet-related genes could be critical for the development and evolution of the spikelet, an evolutionary innovation in the grass family. Likewise, the conceptual discussions on the regulation of a fundamental unit of compound inflorescences could be translated into other organismal groups where compound structures are similarly formed, permitting a comparative perspective on the control of biological complexity.
Friend or foe: Hybrid proline-rich proteins determine how plants respond to beneficial and pathogenic microbes
Authors: Banday Zeeshan Z , Cecchini Nicolás M , Speed DeQuantarius J , Scott Allison T , Parent Claire , Hu Ciara T , Filzen Rachael C , Agbo Elinam , Greenberg Jean T 
Published: June 2022

Abstract
Plant plastids generate signals, including some derived from lipids, that need to be mobilized to effect signaling. We used informatics to discover potential plastid membrane proteins involved in microbial responses in Arabidopsis (Arabidopsis thaliana). Among these are proteins co-regulated with the systemic immunity component AZELAIC ACID INDUCED 1, a hybrid proline-rich protein (HyPRP), and HyPRP superfamily members. HyPRPs have a transmembrane domain, a proline-rich region (PRR), and a lipid transfer protein domain. The precise subcellular location(s) and function(s) are unknown for most HyPRP family members. As predicted by informatics, a subset of HyPRPs has a pool of proteins that target plastid outer envelope membranes via a mechanism that requires the PRR. Additionally, two HyPRPs may be associated with thylakoid membranes. Most of the plastid- and nonplastid-localized family members also have pools that localize to the endoplasmic reticulum, plasma membrane, or plasmodesmata. HyPRPs with plastid pools regulate, positively or negatively, systemic immunity against the pathogen Pseudomonas syringae. HyPRPs also regulate the interaction with the plant growth-promoting rhizobacteria Pseudomonas simiae WCS417 in the roots to influence colonization, root system architecture, and/or biomass. Thus, HyPRPs have broad and distinct roles in immunity, development, and growth responses to microbes and reside at sites that may facilitate signal molecule transport.
Quality Improvement Content in Physical Therapist Education: A Scoping Review
Authors: Struessel Tamara S , Sleddens Nicole M , Jones Katherine J 
Published: June 2022

Abstract

Objective
The purpose of this study was to systematically review the literature regarding teaching quality improvement (QI) in physical therapist education based on the Institute of Medicine’s 6-element definition of QI. Educational activities in QI methods in physical therapist professional education curricula, their developmental stage, and their level of evaluation were described.

Methods
Keywords related to physical therapist students and QI educational activities were used to search studies indexed in PubMed, CINAHL, and ERIC published from 2004 through November 2020. This search yielded 118 studies. After applying inclusion and exclusion criteria, 13 studies were retained for full-text review, which was conducted independently by 2 reviewers. The University of Toronto framework was used to assess developmental stage, and Kirkpatrick’s taxonomy was used to assess the evaluation level of 4 retained studies.

Results
The scope of QI educational activities in the 4 retained studies was limited to 3 of the 6 elements of QI: identifying opportunities for improvement, designing and testing interventions, and identifying errors and hazards in care. None of the studies included educational activities to teach understanding and measuring quality of care. Three of the 4 studies spanned the first 2 stages of the University of Toronto framework (exposure and immersion); 1 study was limited to exposure. None of the studies assessed competence in QI methods. Evaluation of QI education was limited to Kirkpatrick levels 1 (reaction) or 2 (learning). None of the studies evaluated activities at level 3 (transfer of new behaviors) or level 4 (results).

Conclusion
Education in QI methods in professional physical therapist curricula may be limited in scope due to constraints in physical therapist education and the strategic objective of the profession to differentiate itself from other professions.

Impact
Entry-level physical therapists might not be educated to fully participate in interprofessional teams that use QI methods to continuously improve the quality of patient-centered care.
Anti-phosphatidylserine/prothrombin antibodies and thrombosis associate positively with HLA-DRB1*13 and negatively with HLA-DRB1*03 in SLE
Authors: Elbagir Sahwa , Diaz-Gallo Lina-Marcela , Grosso Giorgia , Zickert Agneta , Gunnarsson Iva , Mahler Michael , Svenungsson Elisabet , Rönnelid Johan 
Published: June 2022

Abstract

Objectives
Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1* alleles and thrombosis in SLE. Conventional aPL were included for comparison.

Methods
We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified.

Results
aPS/PT antibodies associated positively with HLA-DRB1*13 [odds ratio (OR) 2.7, P = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1* alleles. HLA-DRB1*13, but not DRB1*04, remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03, on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides.

Conclusions
HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk.
Abnormal timing of slow wave synchronization processes in non-rapid eye movement sleep parasomnias
Authors: Cataldi Jacinthe , Stephan Aurélie M , Marchi Nicola A , Haba-Rubio José , Siclari Francesca 
Published: June 2022

AbstractStudy ObjectivesSleepwalking, confusional arousals, and sleep terrors are parasomnias occurring out of non-rapid eye movement (NREM) sleep. Several previous studies have described EEG changes associated with NREM parasomnia episodes, but it remains unclear whether these changes are specific to parasomnia episodes or whether they are part of the normal awakening process. Here we directly compared regional brain activity, measured with high-density (hd-) EEG, between parasomnia episodes and normal awakenings (without behavioral manifestations of parasomnia).MethodsTwenty adult patients with non-rapid eye movement parasomnias underwent a baseline hd-EEG recording (256 electrodes) followed by a recovery sleep recording after 25 h of total sleep deprivation, during which auditory stimuli were administered to provoke parasomnia episodes.ResultsBoth normal awakenings (n = 25) and parasomnia episodes (n = 96) were preceded by large, steep, and “K-complex-like” slow waves in frontal and central brain regions, and by a concomitant increase in high-frequency EEG (beta) activity. Compared to normal awakenings, parasomnia episodes occurred on a less activated EEG background and displayed higher slow wave activity (SWA) and lower beta activity in frontal and central brain regions after movement onset.ConclusionsOur results suggest that non-rapid eye movement awakenings, irrespective of behavioral manifestations of parasomnia episodes, involve an arousal-related slow wave synchronization process that predominantly recruits frontal and central brain areas. In parasomnia episodes, this synchronization process comes into play abnormally during periods of high SWA and is associated with higher SWA after movement onset. Thus, an abnormal timing of arousal-related slow wave synchronization processes could underlie the occurrence of NREM parasomnias.
Downregulation of miR‐1270 mediates endothelial progenitor cell function in preeclampsia: Role for ATM in the Src/VE‐cadherin axis
Authors: Schröder‐Heurich Bianca , Büder Tim , Meyer Nadia , Vu Thu Huong , Richter Katja , Ramachandran Dhanya , Brodowski Lars , von Kaisenberg Constantin S. , von Versen‐Höynck Frauke 
Published: June 2022

AbstractPreeclampsia, a pregnancy‐related hypertensive disorder, is associated with endothelial dysfunction and increased cardiovascular risk of the offspring in adulthood. In preeclampsia, endothelial colony‐forming cells (ECFC) are reduced in number and function. Recently, we have shown that miR‐1270, which is involved in cancer in vitro proliferation, migration, and tumor progression, is downregulated in fetal ECFC from preeclamptic pregnancies. We now hypothesize that miR‐1270 dysregulation contributes to vascular endothelial dysfunction occurring after preeclampsia via ATM (ataxia telangiectasia mutated) overexpression, the key kinase of DNA damage repair. Here, we show that miR‐1270 silencing in normal ECFC and downregulation in preeclamptic ECFC are accompanied by an increase in the expression levels of ATM. Furthermore, ATM activation correlates with upregulated tyrosine kinase Src leading to phosphorylation and internalization of VE‐cadherin (vascular endothelial‐cadherin) which subsequently compromises endothelial barrier permeability and morphodynamic cell parameters. Treatment with specific ATM inhibitors reveals a novel role of ATM upstream of tyrosine kinase Src activation. Subsequently, Src phosphorylation and internalization of VE‐cadherin compromise endothelial barrier permeability. Our findings suggest that downregulation of miR‐1270 contributes to impaired ECFC function via the associated ATM overexpression, which further identifies ATM as a novel and critical factor for ECFC defects in preeclampsia. Our study provides new insights into the understanding of ECFC impairment associated with cardiovascular risk in preeclamptic offspring and identifies potential novel therapeutic targets.
Financial Incentives for Smoking Cessation in Pregnancy: Multicentre Randomised Controlled Trial
Authors: Berlin Ivan , Berlin Noémi , Malecot Marie , Breton Martine , Jusot Florence , Goldzahl Léontine 
Published: June 2022

(Abstracted from BMJ 2021;375:e065217)
Smoking cessation during pregnancy is important to reduce the risk of adverse pregnancy and birth outcomes. According to the US Preventive Services Task Force, the benefits of behavioral interventions to stop smoking are substantial.
Success Rate of External Cephalic Version in Relation to the Woman's Body Mass Index and Other Factors—A Population-Based Cohort Study
Authors: Svensson Emelie , Axelsson Daniel , Nelson Marie , Nevander Sofia , Blomberg Marie 
Published: June 2022

(Abstracted from Acta Obstet Gynecol Scand 2021;100:2260–2267)
For pregnancies with fetuses in the breech position, external cephalic version (ECV) is used to turn the fetus into a cephalic presentation. The procedure is associated with low complication rates, with the most common being transient fetal heart rate abnormalities, and a success rate up to 65% in various studies.
Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction on Prevention of Small-for-Gestational Age Birth Weights in Newborns Born to At-Risk Pregnant Individuals: The IMPACT BCN Randomized Clinical Trial
Authors: Crovetto Francesca , Crispi Fàtima , Casas Rosa , Martín-Asuero Andrés , Borràs Roger , Vieta Eduard , Estruch Ramon , Gratacós Eduard 
Published: June 2022

(Abstracted from JAMA 2021;326:2150–2160)
Babies with birth weights below the 10th percentile, or small for gestational age infants (SGA), are at risk of poor neurodevelopment or perinatal mortality. Although there is currently no effective prevention therapy for SGA, this study aimed to evaluate the value of structured lifestyle interventions such as a Mediterranean diet or stress reduction therapy in terms of reducing incidence of birth weight <10th percentile and adverse pregnancy outcomes.
Changing Gender Gap and Practice Patterns in Reproductive Endocrinology and Infertility Subspecialists in the United States: A Society for Reproductive Endocrinology and Infertility Report
Authors: Stadtmauer Laurel , Sadek Seifeldin , Richter Kevin S. , Amato Paula , Hurst Bradley S. 
Published: June 2022

(Abstracted from Fertil Steril 2022;117:421–430)
After the implementation of the Equal Pay Act of 1963, the pay gap between men and women for equal work has decreased from 62% to 80%. In the field of medicine, women make up greater than 50% of all students graduating medical school and approximately 40% of faculty members; yet, compared with male counterparts, women continue to be underpaid, obtain less funding, and are promoted at slower and lower rates.