bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual reality curriculum increases paediatric residents’ knowledge of CHDs
Authors: Lim Tiffany R. , Wilson Hunter C. , Axelrod David M. , Werho David K. , Handler Stephanie S. , Yu Sunkyung , Afton Katherine , Lowery Ray , Mullan Patricia B. , Cooke James , Owens Sonal T. 
Published: April 2022

AbstractObjectives:Virtual reality has emerged as a unique educational modality for medical trainees. However, incorporation of virtual reality curricula into formal training programmes has been limited. We describe a multi-centre effort to develop, implement, and evaluate the efficacy of a virtual reality curriculum for residents participating in paediatric cardiology rotations.Methods:A virtual reality software program (“The Stanford Virtual Heart”) was utilised. Users are placed “inside the heart” and explore non-traditional views of cardiac anatomy. Modules for six common congenital heart lesions were developed, including narrative scripts. A prospective case–control study was performed involving three large paediatric residency programmes. From July 2018 to June 2019, trainees participating in an outpatient cardiology rotation completed a 27-question, validated assessment tool. From July 2019 to February 2020, trainees completed the virtual reality curriculum and assessment tool during their cardiology rotation. Qualitative feedback on the virtual reality experience was also gathered. Intervention and control group performances were compared using univariate analyses.Results:There were 80 trainees in the control group and 52 in the intervention group. Trainees in the intervention group achieved higher scores on the assessment (20.4 ± 2.9 versus 18.8 ± 3.8 out of 27 questions answered correctly, p = 0.01). Further analysis showed significant improvement in the intervention group for questions specifically testing visuospatial concepts. In total, 100% of users recommended integration of the programme into the residency curriculum.Conclusions:Virtual reality is an effective and well-received adjunct to clinical curricula for residents participating in paediatric cardiology rotations. Our results support continued virtual reality use and expansion to include other trainees.
Slowing processing speed is associated with cognitive fatigue in newly diagnosed multiple sclerosis patients
Authors: Pitteri Marco , Dapor Caterina , DeLuca John , Chiaravalloti Nancy D. , Marastoni Damiano , Calabrese Massimiliano 
Published: April 2022

AbstractObjective:To further investigate objective measures of cognitive fatigue (CF), defined as the inability to sustain performance over time, in newly diagnosed multiple sclerosis (MS) patients, by conducting a performance analysis on the Paced Auditory Serial Addition Test (PASAT) based on the type of errors (omissions vs. incorrect responses) committed.Method:Sixty-two newly diagnosed patients with MS (pwMS) and 41 healthy controls (HC) completed the PASAT. Analysis of the change in performance during the test was performed by comparing the number of correct responses, incorrect responses, and omissions in the 1st versus the 3rd tertile of the PASAT.Results:A significant decline in accuracy over time was observed to be related to an increment in the number of omissions, significantly more pronounced in pwMS than in HC. No change in the number of incorrect responses throughout the PASAT was observed for either group.Conclusions:CF can be detected even in newly diagnosed pwMS and might objectively manifest as a progressive increase in omissions during a sustained highly demanding task (i.e., PASAT). This pattern may reflect slowed processing speed and increased fatigue in pwMS. Focusing on omissions on the PASAT instead of correct responses only may improve its specificity as an objective measure of CF.
The moderating roles of self-efficacy and depression in dual-task walking in multiple sclerosis: A test of self-awareness theory
Authors: Van Liew Charles , Gudesblatt Mark , Covey Thomas J. , Wilken Jeffrey , Golan Daniel , Zarif Myassar , Bumstead Barbara , Buhse Marijean , Ofori Edward , Peterson Daniel 
Published: April 2022

AbstractObjective:Multiple sclerosis (MS) is a debilitating neurological disease associated with a variety of psychological, cognitive, and motoric symptoms. Walking is among the most important functions compromised by MS. Dual-task walking (DTW), an everyday activity in which people walk and engage in a concurrent, discrete task, has been assessed in MS, but little is known about how it relates to other MS symptoms. Self-awareness theory suggests that DTW may be a function of the interactions among psychological, cognitive, and motor processes.Method:Cognitive testing, self-report assessments for depression and falls self-efficacy (FSE), and walk evaluations [DTW and single-task walk (STW)] were assessed in seventy-three people with MS in a clinical care setting. Specifically, we assessed whether psychological factors (depression and FSE) that alter subjective evaluations regarding one’s abilities would moderate the relationships between physical and cognitive abilities and DTW performance.Results:DTW speed is related to diverse physical and cognitive predictors. In support of self-awareness theory, FSE moderated the relationship between STW and DTW speeds such that lower FSE attenuated the strength of the relationship between them. DTW costs – the change in speed normalized by STW speed – did not relate to cognitive and motor predictors. DTW costs did relate to depressive symptoms, and depressive symptoms moderated the effect of information processing on DTW costs.Conclusions:Findings indicate that an interplay of physical ability and psychological factors – like depression and FSE – may enhance understanding of walking performance under complex, real-world, DTW contexts.
Effect of multiple micronutrient supplements v. iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose
Authors: Gomes Filomena , Agustina Rina , Black Robert E , Christian Parul , Dewey Kathryn G , Kraemer Klaus , Shankar Anuraj H , Smith Emily , Tumilowicz Alison , Bourassa Megan W 
Published: April 2022

AbstractObjective:Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid (IFA) supplements containing 60 mg of Fe. We aimed to assess the effect of MMS v. IFA on neonatal mortality stratified by Fe dose in each supplement.Methods:We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS v. IFA on neonatal mortality in subgroups of trials (n 13) providing the same or different amounts of Fe, that is, MMS with 60 mg of Fe v. IFA with 60 mg of Fe; MMS with 30 mg of Fe v. IFA with 30 mg of Fe; MMS with 30 mg of Fe v. IFA with 60 mg of Fe; and MMS with 20 mg of Fe v. IFA with 60 mg of Fe.Results:There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg v. IFA with 60 mg of Fe (7 trials, 14 114 participants), yielded a non-significant risk ratio of 1·12 (95 % CI 0·83 to 1·50).Conclusion:Neonatal mortality did not differ between MMS and IFA regardless of Fe dose in either supplement.
The bottom-up spillover effect for radical right parties
Authors: Chan Ka Ming 
Published: April 2022

AbstractPrevious literature suggests a party’s electoral result can shape its vote share and calculus of voting in a subsequent election. Less is known about whether this information-updating process helps explain the success of radical right parties (RRPs) in a multi-level system. To answer this question, I use the case of Germany to test whether a bottom-up spillover effect exists for RRPs. Through a regression discontinuity design, I first find that crossing regional electoral hurdles can substantially improve RRPs’ electoral performance in a subsequent general election. Yet, this positive spillover effect cannot be found for other party families. Next, I use a panel to ascertain which mechanisms drive this effect for RRPs. The analysis suggests the legitimation mechanism is more dominant than the viability mechanism and exposure mechanism. These findings enrich our understanding of both the second-order election framework and RRP studies.
(Don’t) bite the hand that feeds you: do critical interest organizations gain less funding in the EU?
Authors: Crepaz Michele , Hanegraaff Marcel 
Published: April 2022

AbstractIn this study we test whether interest organizations that are confrontational towards EU institutions are less successful than their more cooperative counterparts in obtaining funding from the European Commission (EC). The transfer of public funds to interest organizations is a key dynamic in state-civil society relationships. Research shows that organizations, especially public groups, often heavily rely on public funds to the point that, without funds, many would cease to exist. ‘Don’t bite the hand that feeds you’ is thus a popular expression among leaders of organizations who apply for funds. Scholars document a widespread perception among group leaders that a confrontational attitude towards the state can lead to curtail of public funds. This perception is based on the assumption that state institutions use public funding to discipline confrontational interest organizations. We test this assumption using quantitative and qualitative data collected from a survey of 270 interest organizations who applied for EC funding between 2015 and 2018. Our findings suggest that, while almost half of our survey respondents feel that critical attitudes towards the EU would have negative consequences for their funding applications, empirically, confrontational and cooperative organizations have the same chances of obtaining EC grants. This finding is robust across different interest organization categories, including when non-applicants and mortality anxiety are considered in the analysis. The results add a new layer to resource dependency theory pointing at the incongruence between an organization’s perception of its relationship with public institutions and the observation of that relationship.
Differences in Tropical Rainfall in Aquaplanet Simulations With Resolved or Parameterized Deep Convection
Authors: Rios‐Berrios Rosimar , Bryan George H. , Medeiros Brian , Judt Falko , Wang Wei 
Published: April 2022

AbstractThis study investigates the effects of resolved deep convection on tropical rainfall and its multi‐scale variability. A series of aquaplanet simulations are analyzed using the Model for Prediction Across Scales‐Atmosphere with horizontal cell spacings from 120 to 3 km. The 3‐km experiment uses a novel configuration with 3‐km cell spacing between 20°S and 20°N and 15‐km cell spacing poleward of 30°N/S. A comparison of those experiments shows that resolved deep convection yields a narrower, stronger, and more equatorward intertropical convergence zone, which is supported by stronger nonlinear horizontal momentum advection in the boundary layer. There is also twice as much tropical rainfall variance in the experiment with resolved deep convection than in the experiments with parameterized convection. All experiments show comparable precipitation variance associated with Kelvin waves; however, the experiment with resolved deep convection shows higher precipitation variance associated with westward propagating systems. Resolved deep convection also yields at least two orders of magnitude more frequent heavy rainfall rates (>2 mm hr−1) than the experiments with parameterized convection. A comparison of organized precipitation systems demonstrates that tropical convection organizes into linear systems that are associated with stronger and deeper cold pools and upgradient convective momentum fluxes when convection is resolved. In contrast, parameterized convection results in more circular systems, weaker cold pools, and downgradient convective momentum fluxes. These results suggest that simulations with parameterized convection are missing an important feedback loop between the mean state, convective organization, and meridional gradients of moisture and momentum.
Expanded North Pacific Subtropical Gyre and Heterodyne Expression During the Mid‐Pleistocene
Authors: Taylor S. P. , Patterson M. O. , Lam A. R. , Jones H. , Woodard S. C. , Habicht M. H. , Thomas E. K. , Grant G. R. 
Published: April 2022

AbstractThe Kuroshio Current (KC) and Kuroshio Current Extension (KCE) form a western boundary current as part of the North Pacific Subtropical Gyre. This current plays an important role in regulating weather and climate dynamics in the Northern Hemisphere in part by controlling the delivery of moisture to the lower atmosphere. Previous studies indicate the KCE responded dynamically across glacial and interglacial periods throughout the Pliocene‐Pleistocene. However, the response of the KCE during Pleistocene super‐interglacials has not been examined in detail. We present a ∼2.2 Ma record of X‐ray fluorescence elemental data from Ocean Drilling Program Hole 1207A and employ hierarchical clustering techniques to demonstrate paleoenvironmental changes around the KCE. Time‐frequency analysis identifies significant heterodyne frequencies, which suggests there were nonlinear interactions between high‐latitude and low‐latitude climate regulating expansion and contraction of the North Pacific Subtropical Gyre prior to the onset of the Mid‐Pleistocene Climate Transition (MPT). We observe two periods of elevated ln Ca/Ti, which may represent sustained warmth with northward migrations of the KCE in the northwestern Pacific. These intervals correspond to Marine Isotope Stages 29‐25, 15, and 11‐9 and occur around recent climatic transitions, the MPT and Mid‐Brunhes Event. Northward expansion of the subtropical gyre during these exceptionally warm interglacials would have delivered more heat and moisture to the high latitudes of the northwest Pacific. Furthermore, enhanced evaporation from the warm KCE vented to the lower atmosphere may have preconditioned the Northern Hemisphere for ice volume growth during two of the most recent periods of climate transition.
Human herpesvirus 8 infection is associated with prostate cancer among IFNL4-ΔG carriers
Authors: Jenkins Frank J. , Minas Tsion Z. , Tang Wei , Dorsey Tiffany H. , Ambs Stefan 
Published: April 2022

Abstract
Background
The dinucleotide germline variant, rs368234815-ΔG, in the IFNL4 gene (IFNL4-ΔG) has been associated with prostate cancer among men at increased risk of sexually transmitted infections and reported to impair viral clearance. Human herpesvirus 8 (HHV-8) seropositivity has been associated with prostate cancer in Tobago.

Methods
We examined whether the association of HHV-8 with prostate cancer is IFNL4-ΔG-dependent among 728 IFNL4-ΔG-genotyped cases and 813 genotyped population-based controls from the NCI-Maryland Prostate Cancer Case-Control study. Associations between HHV-8 and prostate cancer were assessed in multivariable unconditional logistic regression models. We calculated adjusted odds ratios (OR) and stratified the analysis into men harboring the IFNL4-ΔG-variant and non-carriers (ΔG/ΔG or ΔG/TT vs. TT/TT).

Results
HHV-8 seropositivity was higher in cases than controls (11% vs. 6%) and this association was restricted to carriers of the ΔG allele (OR 2.19: 95% CI:1.38–3.48) in both African American (OR 1.96; 95% CI:1.08–3.56) and European American men (OR 2.59; 95% CI:1.20–5.56).

Conclusions
HHV-8 seropositivity is associated with increased odds of prostate cancer in men harboring the IFNL4 rs368234815-ΔG variant. This study describes HHV-8 infection as a candidate prostate cancer risk factor in men with the IFNL4-ΔG genotype and supports the hypothesis that IFNL4-ΔG is a susceptibility factor that contributes to prostate cancer.
PRKDC promotes hepatitis B virus transcription through enhancing the binding of RNA Pol II to cccDNA
Authors: Fan Yao , Liang Yi , Liu Yu , Fan Hui 
Published: April 2022

AbstractHepatitis B virus infection remains a major health problem worldwide due to its high risk of liver failure and hepatocellular carcinoma. Covalently closed circular DNA (cccDNA), which is present as an individual minichromosome, serves as the template for transcription of all viral RNAs and pla ays critical role in viral persistence. Therefore, there is an urgent need to gain broader insight into the transcription regulation of cccDNA. Here, we combined a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) with an engineered ascorbate peroxidase 2 (APEX2) to identify cccDNA associated proteins systematically in living cells. By functional screening, we verified that protein kinase, DNA-activated, catalytic subunit (PRKDC) was an effective activator of HBV cccDNA transcription in HBV-infected HepG2-NTCP cells and primary human hepatocytes. Mechanismly, PRKDC interacted with POLR2A and POLR2B, the two largest subunits of RNA polymerase II (Pol II) and recruited Pol II to HBV cccDNA minichromosome in a kinase-dependent manner. PRKDC knockdown or inhibitor treatment significantly decreased the enrichment of POLR2A and POLR2B on cccDNA, as well as reducing the levels of cccDNA associated Pol II Ser5 and Ser2 phosphorylation, which eventually inhibited the HBV cccDNA activity. Collectively, these findings give us new insights into cccDNA transcription regulation, thus providing new potential targets for HBV treatment in patients.
JMJD2C mediates the MDM2/p53/IL5RA axis to promote CDDP resistance in uveal melanoma
Authors: Zhu Qi , Chen Han , Li Xiaoying , Wang Xi , Yan Hongtao 
Published: April 2022

AbstractChemotherapy resistance poses an obstacle for effective treatment of uveal melanoma. In this study, we aim to investigate the effects of jumonji domain containing 2C (JMJD2C)-mediated mouse double minute-2 homolog (MDM2)/p53/interleukin 5 receptor subunit alpha (IL5RA) axis on cisplatin (CDDP) resistance in uveal melanoma. RT-qPCR and Western blot assay were performed to determine their expression patterns in uveal melanoma cell line (MUM-2B) and CDDP-resistant cell line (MUM-2B/CDDP). The enrichment of H3K9me3 in MDM2 promoter region was examined by ChIP, and the binding between p53 and ubiquitin in MUM-2B cells testified by co-IP assay. Following overexpression or silencing of JMJD2C/MDM2/p53/IL5RA, the 50% concentration of inhibition (IC50) and the biological characteristics of MUM-2B and MUM-2B/CDDP cells were examined using CCK-8 assay, SA-β-gal staining, fluorescence-activated cell sorting analysis, and Transwell assay. Finally, the tumorigenicity of transplanted MUM-2B and MUM-2B/CDDP cells in nude mice was assessed. JMJD2C was documented to be highly expressed in uveal melanoma cells, promoting the CDDP resistance. Histone demethylase JMJD2C removed the H3K9me3 modification of MDM2 promoter, which promoted the expression of MDM2. MDM2 enhanced the IL5RA expression through stimulating the ubiquitination and degradation of p53, thus inducing CDDP resistance of uveal melanoma cells. Furthermore, the results of in vivo experiments revealed that JMJD2C mediated the MDM2/p53/IL5RA axis to expedite the growth of uveal melanoma and augment the CDDP resistance. Taken together, JMJD2C can induce histone demethylation to upregulate MDM2, thereby ubiquitinating p53 and upregulating IL5RA. As a consequence, CDDP resistance in uveal melanoma is ultimately accelerated.
A structural exposé of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop
Authors: Wang Huanchen , Perera Lalith , Jork Nikolaus , Zong Guangning , Riley Andrew M. , Potter Barry V. L. , Jessen Henning J. , Shears Stephen B. 
Published: April 2022

AbstractStructural snapshots of protein/ligand complexes are a prerequisite for gaining atomic level insight into enzymatic reaction mechanisms. An important group of enzymes has been deprived of this analytical privilege: members of the protein tyrosine phosphatase (PTP) superfamily with catalytic WPD-loops lacking the indispensable general-acid/base within a tryptophan-proline-aspartate/glutamate context. Here, we provide the ligand/enzyme crystal complexes for one such PTP outlier: Arabidopsis thaliana Plant and Fungi Atypical Dual Specificity Phosphatase 1 (AtPFA-DSP1), herein unveiled as a regioselective and efficient phosphatase towards inositol pyrophosphate (PP-InsP) signaling molecules. Although the WPD loop is missing its canonical tripeptide motif, this structural element contributes to catalysis by assisting PP-InsP delivery into the catalytic pocket, for a choreographed exchange with phosphate reaction product. Subsequently, an intramolecular proton donation by PP-InsP substrate is posited to substitute functionally for the absent aspartate/glutamate general-acid. Overall, we expand mechanistic insight into adaptability of the conserved PTP structural elements.
An unexpected strategy to alleviate hypoxia limitation of photodynamic therapy by biotinylation of photosensitizers
Authors: An Jing , Tang Shanliang , Hong Gaobo , Chen Wenlong , Chen Miaomiao , Song Jitao , Li Zhiliang , Peng Xiaojun , Song Fengling , Zheng Wen-Heng 
Published: April 2022

AbstractThe most common working mechanism of photodynamic therapy is based on high-toxicity singlet oxygen, which is called Type II photodynamic therapy. But it is highly dependent on oxygen consumption. Recently, Type I photodynamic therapy has been found to have better hypoxia tolerance to ease this restriction. However, few strategies are available on the design of Type I photosensitizers. We herein report an unexpected strategy to alleviate the limitation of traditional photodynamic therapy by biotinylation of three photosensitizers (two fluorescein-based photosensitizers and the commercially available Protoporphyrin). The three biotiylated photosensitizers named as compound 1, 2 and 3, exhibit impressive ability in generating both superoxide anion radicals and singlet oxygen. Moreover, compound 1 can be activated upon low-power white light irradiation with stronger ability of anion radicals generation than the other two. The excellent combinational Type I / Type II photodynamic therapy performance has been demonstrated with the photosensitizers 1. This work presents a universal protocol to provide tumor-targeting ability and enhance or trigger the generation of anion radicals by biotinylation of Type II photosensitizers against tumor hypoxia.