bluuebunny/crossref_metadata_2025_split huggingface dataset:
A loosened gating mechanism of RIG-I leads to autoimmune disorders
Authors: Lei Yixuan , Fei Panyu , Song Bin , Shi Wenjia , Luo Cheng , Luo Dahai , Li Dan , Chen Wei , Zheng Jie 
Published: April 2022

AbstractDDX58 encodes RIG-I, a cytosolic RNA sensor that ensures immune surveillance of nonself RNAs. Individuals with RIG-IE510V and RIG-IQ517H mutations have increased susceptibility to Singleton-Merten syndrome (SMS) defects, resulting in tissue-specific (mild) and classic (severe) phenotypes. The coupling between RNA recognition and conformational changes is central to RIG-I RNA proofreading, but the molecular determinants leading to dissociated disease phenotypes remain unknown. Herein, we employed hydrogen/deuterium exchange mass spectrometry (HDX-MS) and single molecule magnetic tweezers (MT) to precisely examine how subtle conformational changes in the helicase insertion domain (HEL2i) promote impaired ATPase and erroneous RNA proofreading activities. We showed that the mutations cause a loosened latch-gate engagement in apo RIG-I, which in turn gradually dampens its self RNA (Cap2 moiety:m7G cap and N1-2-2′-O-methylation RNA) proofreading ability, leading to increased immunopathy. These results reveal HEL2i as a unique checkpoint directing two specialized functions, i.e. stabilizing the CARD2-HEL2i interface and gating the helicase from incoming self RNAs; thus, these findings add new insights into the role of HEL2i in the control of antiviral innate immunity and autoimmunity diseases.
Guillain-Barre syndrome complicating Neisseria meningitidis infection
Authors: Khangarot Digvijay , Panegyres Peter K 
Published: April 2022

Abstract
Guillain-Barré Syndrome (GBS)—an immune-mediated condition—is the most common cause of acute flaccid paralysis, since the elimination of poliomyelitis. We present a case of GBS as a rare complication of meningococcal meningitis based on clinical features, nerve conduction studies and magnetic resonance imaging (MRI) findings. GBS has rarely been described after meningitis. This case is unique in that our findings show that GBS may be observed after meningococcal meningitis.
Topical Endoxifen for Mammographic Density Reduction—A Randomized Controlled Trial
Authors: Bäcklund Magnus , Eriksson Mikael , Gabrielson Marike , Hammarström Mattias , Quay Steve , Bergqvist Jenny , Hellgren Roxanna , Czene Kamila , Hall Per 
Published: April 2022

Abstract
Although breast cancer incidence is increasing, there are few primary preventive initiatives. Tamoxifen can reduce breast cancer incidence but is rarely used for primary prevention due to adverse events and tolerance issues. We tested if endoxifen, a tamoxifen metabolite, applied directly to the skin of the breast, could reduce mammographic density, a proxy for therapy response. Ninety women were randomized to placebo, 10 and 20 mg of topical Z-endoxifen for 6 months. Mammographic density and symptoms were measured at baseline and study exit. Despite a high discontinuation rate, driven by skin rashes, we found a significant mammographic density decrease, a dose-dependent increase in the concentration of plasma Z-endoxifen but no systemic side effects. Topical application of tamoxifen metabolites has the potential to decrease breast cancer incidence without major systemic side effects. However, endoxifen may not be suitable for topical administration and is unlikely to be used for breast cancer prevention.
SAUR15 interaction with BRI1 activates plasma membrane H+-ATPase to promote organ development of Arabidopsis
Authors: Li Mengzhan , Liu Chunli , Hepworth Shelley R , Ma Chaofan , Li Hong , Li Jia , Wang Suo-Min , Yin Hongju 
Published: April 2022

Abstract
Brassinosteroids (BRs) are an important group of plant steroid hormones that regulate growth and development. Several members of the SMALL AUXIN UP RNA (SAUR) family have roles in BR-regulated hypocotyl elongation and root growth. However, the mechanisms are unclear. Here, we show in Arabidopsis (Arabidopsis thaliana) that SAUR15 interacts with cell surface receptor-like kinase BRASSINOSTEROID-INSENSITIVE 1 (BRI1) in BR-treated plants, resulting in enhanced BRI1 phosphorylation status and recruitment of the co-receptor BRI1-ASSOCIATED RECEPTOR KINASE 1. Genetic and phenotypic assays indicated that the SAUR15 effect on BRI1 can be uncoupled from BRASSINOSTEROID INSENSITIVE 2 activity. Instead, we show that SAUR15 promotes BRI1 direct activation of plasma membrane H+-ATPase (PM H+-ATPase) via phosphorylation. Consequently, SAUR15–BRI1–PM H+-ATPase acts as a direct, PM-based mode of BR signaling that drives cell expansion to promote the growth and development of various organs. These data define an alternate mode of BR signaling in plants.
Transcription factors BBX11 and HY5 interdependently regulate the molecular and metabolic responses to UV-B
Authors: Job Nikhil , Lingwan Maneesh , Masakapalli Shyam Kumar , Datta Sourav 
Published: April 2022

Abstract
UV-B radiation acts as a developmental cue and a stress factor for plants, depending on dose. Activation of the transcription factor ELONGATED HYPOCOTYL 5 (HY5) in a UV RESISTANCE LOCUS 8 (UVR8)-dependent manner leads to the induction of a broad set of genes under UV-B. However, the underlying molecular mechanisms regulating this process are less understood. Here, we use molecular, biochemical, genetic, and metabolomic tools to identify the B-BOX transcription factor B-BOX PROTEIN 11 (BBX11) as a component of the molecular response to UV-B in Arabidopsis (Arabidopsis thaliana). BBX11 expression is induced by UV-B in a dose-dependent manner. Under low UV-B, BBX11 regulates hypocotyl growth suppression, whereas it protects plants exposed to high UV-B radiation by promoting the accumulation of photo-protective phenolics and antioxidants, and inducing DNA repair genes. Our genetic studies indicate that BBX11 regulates hypocotyl elongation under UV-B partially dependent on HY5. Overexpression of BBX11 can partially rescue the high UV-B sensitivity of hy5, suggesting that HY5-mediated UV-B stress tolerance is partially dependent on BBX11. HY5 regulates the UV-B-mediated induction of BBX11 by directly binding to its promoter. BBX11 reciprocally regulates the mRNA and protein levels of HY5. We report here the role of a BBX11-HY5 feedback loop in regulating photomorphogenesis and stress tolerance under UV-B.
Graph Convolutional Networks Reveal Network-Level Functional Dysconnectivity in Schizophrenia
Authors: Lei Du , Qin Kun , Pinaya Walter H L , Young Jonathan , Van Amelsvoort Therese , Marcelis Machteld , Donohoe Gary , Mothersill David O , Corvin Aiden , Vieira Sandra , Lui Su , Scarpazza Cristina , Arango Celso , Bullmore Ed , Gong Qiyong , McGuire Philip , Mechelli Andrea 
Published: April 2022

AbstractBackground and HypothesisSchizophrenia is increasingly understood as a disorder of brain dysconnectivity. Recently, graph-based approaches such as graph convolutional network (GCN) have been leveraged to explore complex pairwise similarities in imaging features among brain regions, which can reveal abstract and complex relationships within brain networks.Study DesignWe used GCN to investigate topological abnormalities of functional brain networks in schizophrenia. Resting-state functional magnetic resonance imaging data were acquired from 505 individuals with schizophrenia and 907 controls across 6 sites. Whole-brain functional connectivity matrix was extracted for each individual. We examined the performance of GCN relative to support vector machine (SVM), extracted the most salient regions contributing to both classification models, investigated the topological profiles of identified salient regions, and explored correlation between nodal topological properties of each salient region and severity of symptom.Study ResultsGCN enabled nominally higher classification accuracy (85.8%) compared with SVM (80.9%). Based on the saliency map, the most discriminative brain regions were located in a distributed network including striatal areas (ie, putamen, pallidum, and caudate) and the amygdala. Significant differences in the nodal efficiency of bilateral putamen and pallidum between patients and controls and its correlations with negative symptoms were detected in post hoc analysis.ConclusionsThe present study demonstrates that GCN allows classification of schizophrenia at the individual level with high accuracy, indicating a promising direction for detection of individual patients with schizophrenia. Functional topological deficits of striatal areas may represent a focal neural deficit of negative symptomatology in schizophrenia.
The Social Scientific Turn in Modern British History
Authors: Butler Lise 
Published: April 2022

Abstract
In recent decades, scholars of modern British history have increasingly revisited the classic social science of the post-war period. Within this ‘social scientific turn’ in modern British history we can discern closely-related but distinct strands of work. One group of historians, influenced by intellectual history and political history methods, have examined how post-war social science and social scientists have shaped modern British politics and culture. Other historians have engaged closely with the original research materials of post-war social science as source bases for understanding lived experience, and explored the gulf between how sociologists and researchers talked about people, and how they understood themselves. Understanding the different aims and methods with which modern British historians have engaged with post-war social research is essential to understanding the methodology and value of the ‘social scientific turn’ in modern British history today.
Systematics and phylogeography of western Mediterranean tarantulas (Araneae: Theraphosidae)
Authors: Korba Jan , Opatova Vera , Calatayud-Mascarell Arnau , Enguídanos Alba , Bellvert Adrià , Adrián Silvia , Sánchez-Vialas Alberto , Arnedo Miquel A 
Published: April 2022

AbstractTheraphosidae is the most diversified family of mygalomorph spiders, commonly known as tarantulas. Two genera inhabit the Mediterranean region: Chaetopelma in the east and Ischnocolus mostly in the western part of the Basin. Their phylogenetic position and the validity of some Ischnocolus species remain unclear. We implemented a multilocus target approach to shed new light on the position of both genera and further integrated molecular data with additional lines of evidence (morphology and ecology) to explore species boundaries in western Mediterranean Ischnocolus. Our results reveal that Ischnocolus and Chaetopelma are not closely related. Chaetopelma formed a clade with the African subfamily Eumenophorinae and Ischnocolus was recovered in a clade comprising all remaining theraphosids. The western Mediterranean Ischnocolus comprises two deeply divergent clades that separated during the Early Miocene and differ in both morphology and lifestyle. We found molecular, morphological and ecological evidence to restore the name Ischnocolus mogadorensis and revalidate this species. We also uncovered distinct allopatric lineages in Ischnocolus elongatus. However, the lack of males, the uniform morphology of females and low within-clade support hampered the assessment of their status and boundaries. Finally, our data support that I. elongatus should be considered a senior synonym of Ischnocolus hancocki and Harpactirella insidiosa.
Mechanisms Driving Postgraduate Health and Social Science Students’ Cultural Competence: An Integrated Systematic Review
Authors: Lie Ken Jie Christopher , Finn Yvonne F. , Bish Melanie , Carlson Elisabeth , Kumlien Christine , Chan E. Angela , Leung Doris Y.L. 
Published: April 2022

Purpose
The COVID-19 pandemic revealed a global urgency to address health care provision disparities, which have largely been influenced by systematic racism in federal and state policies. The World Health Organization recommends educational institutions train clinicians in cultural competence (CC); however, the mechanisms and interacting social structures that influence individuals to achieve CC have received little attention. This review investigates how postgraduate health and social science education approaches CC and how it accomplishes (or not) its goals.

Method
The authors used critical realism and Whittemore and Knafl’s methods to conduct a systematic integrated review. Seven databases (MEDLINE, CINAHL, PsycINFO, Scopus, PubMed, Web of Science, and ERIC) were searched from 2000 to 2020 for original research studies. Inclusion criteria were: the use of the term “cultural competence” and/or any one of Campinha-Bacote’s 5 CC factors, being about postgraduate health and/or social science students, and being about a postgraduate curriculum or a component of it. Thematic analysis was used to reveal the mechanisms and interacting social structures underlying CC.

Results
Thirty-two studies were included and 2 approaches to CC (themes) were identified. The first theme was professionalized pedagogy, which had 2 subthemes: othering and labeling. The second theme was becoming culturally competent, which had 2 subthemes: a safe CC teaching environment and social interactions that cultivate reflexivity.

Conclusions
CC conceptualizations in postgraduate health and social science education tend to view cultural differences as a problem and CC skills as a way to mitigate differences to enhance patient care. However, this generates a focus on the other, rather than a focus on the self. Future research should explore the extent to which insight, cognitive flexibility, and reflexivity, taught in safe teaching environments, are associated with increasing students’ cultural safety, cultural humility, and CC.
Blastic Indeterminate Dendritic Cell Tumor Associated With Chronic Myelomonocytic Leukemia
Authors: Ellis Austin , Elbaz Younes Ismail , Shao Haipeng , Zhang Xiaohui 
Published: April 2022

Abstract:
Indeterminate dendritic cell tumor (IDCT) is an exceedingly rare neoplasm that can be associated with hematopoietic malignancies. We report a case of multifocal cutaneous blastic indeterminate dendritic cell tumor (BIDCT) in a 75-year-old man with chronic myelomonocytic leukemia showing blastic histiocytoid morphology, positivity for CD1a and S100, and no expression of langerin. We present a literature review on the 11 reported cases of IDCTs/BIDCTs associated with chronic myelomonocytic leukemia (CMML), including this case. The clinicopathological characteristics have been summarized. The IDCT and CMML cells are clonally related in 4 tested cases. Patients with IDCT/BIDCT associated with CMML seem to have worse clinical outcomes compared with patients with IDCT not associated with CMML.
Diagnostic Performance of Optical Coherence Tomography for Pseudoexfoliation Glaucoma
Authors: Ozcelik-Kose Alev , Yıldız Merve Beyza , Imamoglu Serhat 
Published: April 2022

Precis:
LC thickness and LCCI had comparable diagnostic performances with RNFL thickness in distinguishing eyes with PXG from those with PXS. BMO-MRW showed the lowest diagnostic performance among all geometric parameters derived from OCT scans we evaluated.

Objective:
To compare the diagnostic performance of different geometric parameters derived from optical coherence tomography (OCT) scans (retinal nerve fiber layer [RNFL] thickness, lamina cribrosa [LC] thickness, LC curvature index [LCCI] and Bruch’s membrane opening-minimum rim width [BMO-MRW]) for distinguishing eyes with pseudoexfoliation glaucoma (PXG) from pseudoexfoliation syndrome (PXS) and healthy eyes.

Methods:
Fifty-five eyes of 55 patients with PXG, 55 eyes of 55 patients with PXS, and 50 healthy subjects were enrolled in this cross-sectional study. The areas under the receiver operating characteristic curves (AUCs) of RNFL thickness, LC thickness, LCCI and BMO-MRW were calculated and compared.

Results:
In discriminating between eyes with PXG from those with PXS, LC thickness (0.930 [95% CI: 0.883–0.978]) and global RNFL thickness (0.974 [95% CI: 0.947–0.992]) presented comparable AUCs (P=0.244). In distinguishing subjects wiht PXG from healthy controls, both LC thickness (0.972 [95% CI: 0.948–0.997]) and LCCI (0.983 [95% CI: 0.968–0.998]) had comparable AUCs with global RNFL thickness (0.988 [95% CI: 0.974–1.000]) (P=0.094 andP=0.239, respectively). Global BMO-MRW had lower AUCs than RNFL thickness (0.839 [95% CI: 0.759–0.920] and 0.897 [95% CI: 0.836–0.958], respectively) in distinguishing PXG from both PXS and healthy controls (P=0.001 andP=0.002, respectively). BMO-MRW also had significantly lower AUCs than both LC thickness and LCCI in distinguishing PXG from healthy controls (P=0.034 andP=0.001, respectively).

Conclusion:
LC thickness and LCCI had better diagnostic performance than BMO-MRW in distinguishing PXG from PXS and healthy controls, which were comparable to RNFL thickness.
Acute Hyperkinetic Movement Disorders as a Multifactorial Pharmacodynamic Drug Interaction Between Methylphenidate and Risperidone in Children and Adolescents
Authors: Mohamoud Mohamed , Chen Qi , Croteau David , Cheng Carmen , Burkhart Keith , Volpe Donna A. , Kortepeter Cindy , Demczar Dorothy , Stone Marc 
Published: April 2022

Abstract

Purpose/Background
Acute hyperkinetic movement disorders have been reported with the concomitant use of attention-deficit/hyperactivity disorder (ADHD) stimulants and antipsychotics in children and adolescents. We analyzed postmarketing reports of suspected acute hyperkinetic movement disorder associated with concomitant use of ADHD stimulants and antipsychotics.

Methods/Procedures
We searched for postmarketing reports of acute hyperkinetic movement disorders associated with concomitant use of ADHD stimulants-antipsychotics in the US Food and Drug Administration Adverse Event Reporting System through December 6, 2019. PubMed and EMBASE were also searched for acute hyperkinetic movement reports with the concomitant use of ADHD stimulants-antipsychotics through January 13, 2020.

Findings/Results
We identified 36 cases resulting in acute hyperkinetic movement disorder associated with the concomitant use of ADHD stimulants-antipsychotics, 19 of which were also identified in the medical literature. From an ADHD stimulant perspective, methylphenidate products accounted for the largest number of cases (n = 23 [64%]), followed by amphetamine products (n = 9 [25%]) and atomoxetine (n = 4 [11%]). From an antipsychotic perspective, all 36 cases were reported with second-generation antipsychotics, particularly risperidone (n = 20 [56%]). Most of the cases were reported in boys (n = 31 [86%]) aged 6 to 12 years (n = 27 [75%]). Approximately 53% of the cases reported a time to onset within 24 hours of the drug change. Acute dystonic reactions (n = 27 [75%]) were the most frequently reported movement disorder.

Implications/Conclusions
As outlined in changes to the US prescribing information for all methylphenidate and risperidone products, health care professionals should be aware that changes to this combination may be associated with a pharmacodynamic drug-drug interaction resulting in acute hyperkinetic movement disorder.
Central Nervous System Trial Failures
Authors: Grabb Margaret C. , Potter William Z. 
Published: April 2022

Abstract

Purpose/Background
Drug trials of the central nervous system(CNS) have been plagued with uninformative failures, often because of the difficulties of knowing definitively whether dosing achieved was sufficient to modulate the intended CNS target at adequate concentrations to produce pharmacodynamic or dose-related changes in readouts of brain function. Key design elements can be introduced into early-stage trials to get at this issue.

Methods/Procedures
This commentary builds on a review of earlier clinical studies in Fragile X syndrome to explore the extent to which the chain of evidence is in place to allow for interpretation of the results as ruling in or out the utility of modulating one or another molecular target to treat this disorder. Recent and current biomarker studies in Fragile X syndrome occurring subsequent to the clinical studies are reviewed to see if they might address any chain of evidence gaps.

Findings/Results
Despite the strong preclinical basis for targeting molecular mechanisms, the lack of efficacy seen in clinical studies remains uninterpretable, with regard to ruling in or out the utility of targeting the mechanism in a clinical population, given the absence of studies, which address whether doses of administered drug impacted the targeted brain mechanism.

Implications/Conclusions
The value of pursuing clinical studies of compounds targeted to novel mechanisms in the absence of clinical pharmacological evidence of some anticipated mediating pharmacokinetic/pharmacodynamic signals is questionable. One or more biomarkers of a drug effect on brain function are needed to establish dose dependent CNS effects that allow one to interpret clinical results as ruling in or out a mechanism and providing a firm basis for continuing or not, as well as informing dose selection in any clinical efficacy trials. Initiatives to address this general need in pediatric psychopharmacology are highlighted.
Place of Birth Preferences and Relationship to Maternal and Newborn Outcomes Within the American Association of Birth Centers Perinatal Data Registry, 2007-2020
Authors: Jolles Diana R. , Montgomery Tiffany M. , Blankstein Breman Rachel , George Erin , Craddock Jaih , Sanders Sarah , Niemcyzk Nancy , Stapleton Susan , Bauer Kate , Wright Jennifer 
Published: April 2022

Purpose:
The purpose of this study was to describe sociodemographic variations in client preference for birthplace and relationships to perinatal health outcomes.

Methods:
Descriptive data analysis (raw number, percentages, and means) showed that preference for birthplace varied across racial and ethnic categories as well as sociodemographic categories including educational status, body mass index, payer status, marital status, and gravidity. A subsample of medically low-risk childbearing people, qualified for birth center admission in labor, was analyzed to assess variations in maternal and newborn outcomes by site of first admission in labor.

Results:
While overall clinical outcomes exceeded national benchmarks across all places of admission in the sample, disparities were noted including higher cesarean birth rates among Black and Hispanic people. This variation was larger within the population of people who preferred to be admitted to the hospital in labor in the absence of medical indication.

Conclusion:
This study supports that the birth center model provides safe delivery care across the intersections of US sociodemographics. Findings from this study highlight the importance of increased access and choice in place of birth for improving health equity, including decreasing cesarean birth and increasing breastfeeding initiation.