bluuebunny/crossref_metadata_2025_split huggingface dataset:
The E3 ubiquitin ligases SINA1 and SINA2 integrate with the protein kinase CIPK20 to regulate the stability of RGL2a, a positive regulator of anthocyanin biosynthesis
Authors: An Jian‐Ping , Zhang Xiao‐Wei , Li Hong‐Liang , Wang Da‐Ru , You Chun‐Xiang , Han Yuepeng 
Published: May 2023

Summary
Although DELLA protein destabilization mediated by post‐translational modifications is essential for gibberellin (GA) signal transduction and GA‐regulated anthocyanin biosynthesis, the related mechanisms remain largely unknown. In this study, we report the ubiquitination and phosphorylation of an apple DELLA protein MdRGL2a in response to GA signaling and its regulatory role in anthocyanin biosynthesis.
MdRGL2a could interact with MdWRKY75 to enhance the MdWRKY75‐activated transcription of anthocyanin activator MdMYB1 and interfere with the interaction between anthocyanin repressor MdMYB308 and MdbHLH3 or MdbHLH33, thereby promoting anthocyanin accumulation.
A protein kinase MdCIPK20 was found to phosphorylate and protect MdRGL2a from degradation, and it was essential for MdRGL2a‐promoting anthocyanin accumulation. However, MdRGL2a and MdCIPK20 were ubiquitinated and degraded by E3 ubiquitin ligases MdSINA1 and MdSINA2, respectively, both of which were activated in the presence of GA.
Our results display the integration of SINA1/2 with CIPK20 to dynamically regulate GA signaling and will be helpful toward understanding the mechanism of GA signal transduction and GA‐inhibited anthocyanin biosynthesis. The discovery of extensive interactions between DELLA and SINA and CIPK proteins in apple will provide reference for the study of ubiquitination and phosphorylation of DELLA proteins in other species.
Personality traits, democratic support, and authoritarian nostalgia
Authors: Kim‐Leffingwell Sanghoon 
Published: May 2023

AbstractObjectiveWhy do democratic voters feel nostalgia for an authoritarian past? This article introduces a dispositional framework for authoritarian nostalgia, showing that in addition to situational factors, an enduring source of sentimental longing for the authoritarian past may very well be rooted in a person's core psychological structure.MethodsI use mixed‐methods approach with data collection from South Korea and Taiwan. Using linear regression models with interaction terms, I analyze the contingent effects of personality traits on authoritarian nostalgia.ResultsI find that people high in emotional stability are likely to be nostalgic and that the trait's effects are greater than those from other traits traditionally associated with authoritarian ideology. Results from the interaction model show that these impacts are more pronounced with weak and moderate democrats but not with strong democrats.ConclusionPeople high in emotional stability are nostalgic due to their longing for the proven socioeconomic performance of the past. In addition, the democratic values of individual citizens can constrict how personality shapes voters’ view of former dictatorships.
Etudes for the inverse spectral problem
Authors: Makarov Nikolai , Poltoratski Alexei 
Published: May 2023

AbstractIn this note, we study inverse spectral problems for canonical Hamiltonian systems, which encompass a broad class of second‐order differential equations on a half‐line. Our goal is to extend the classical results developed in the work of Marchenko, Gelfand–Levitan, and Krein to broader classes of canonical systems and to illustrate the solution algorithms and formulae with a variety of examples. One of the main ingredients of our approach is the use of truncated Toeplitz operators, which complement the standard toolbox of the Krein–de Branges theory of canonical systems.
Caffeine Enhances 10-km Cycling Performance in Habitual Users Only When Preceded by Caffeine Abstinence
Authors: Griest Timothy D. , Saunders Michael J. , Womack Christopher J. , Luden Nicholas D. 
Published: May 2023

Purpose: The primary objective was to assess the performance benefits of caffeine (CAF) supplementation in habitual users. Importantly, this investigation was designed to account for the potential confounding effects of CAF withdrawal (CAFW), which are inherent and common in previous work. Methods: Ten CAF-consuming (394 [146] mg·d−1) recreational cyclists (age 39.1 [14.9] y; maximum oxygen consumption 54.2 [6.2] mL·kg–1·min–1) completed four 10-km time trials (TTs) on a cycle ergometer. On each trial day, 8 hours before reporting to the laboratory, subjects consumed 1.5 mg·kg–1 CAF to prevent withdrawal (no withdrawal [N]) or a placebo (PLA; withdrawal [W]). Then, 1 hour prior to exercise, they received either 6 mg·kg–1 CAF or PLA. These protocols were repeated 4 times, employing all combinations of N/W and CAF/PLA. Results: CAFW did not impair TT power output (PLAW vs PLAN P = .13). However, preexercise CAF only improved TT performance when compared to PLA in the W condition (CAFN vs PLAW P = .008, CAFW vs PLAW P = .04), not when W was mitigated (PLAN vs CAFN P = .33). Conclusions: These data indicate that preexercise CAF only improves recreational cycling performance when compared to bouts preceded by CAF abstinence, suggesting that habitual users may not benefit from 6 mg·kg–1 of CAF and that previous work may have overstated the value of CAF supplementation for habitual users. Future work should examine higher doses of CAF for habitual users.
Insulin resistance, age and depression’s impact on cognition in middle-aged adults from the PREVENT cohort
Authors: Bauermeister Sarah D , Ben Yehuda Michael , Reid Graham , Howgego Gregory , Ritchie Karen , Watermeyer Tam , Gregory Sarah , Terrera Graciela Muniz , Koychev Ivan 
Published: May 2023

BackgroundAlzheimer’s disease (AD), type 2 diabetes mellitus (characterised by insulin resistance) and depression are significant challenges facing public health. Research has demonstrated common comorbidities among these three conditions, typically focusing on two of them at a time.ObjectiveThe goal of this study, however, was to assess the inter-relationships between the three conditions, focusing on mid-life (defined as age 40–59) risk before the emergence of dementia caused by AD.MethodsIn the current study, we used cross-sectional data from 665 participants from the cohort study, PREVENT.FindingsUsing structural equation modelling, we showed that (1) insulin resistance predicts executive dysfunction in older but not younger adults in mid-life, that (2) insulin resistance predicts self-reported depression in both older and younger middle-aged adults and that (3) depression predicts deficits in visuospatial memory in older but not younger adults in mid-life.ConclusionsTogether, we demonstrate the inter-relations between three common non-communicable diseases in middle-aged adults.Clinical implicationsWe emphasise the need for combined interventions and the use of resources to help adults in mid-life to modify risk factors for cognitive impairment, such as depression and diabetes.
Interactions between Australian cancer physicians and the pharmaceutical industry: a qualitative study
Authors: Pokorny Adrian M J , Bero Lisa A , Fox Peter , Karikios Deme J , McEwin Eliza J , Moynihan Ray , Mintzes Barbara 
Published: May 2023

ObjectivesTo understand how and why Australian cancer physicians interact with the pharmaceutical industry.DesignQualitative study using semistructured interviews, performed by a medical oncologist. Thematic analysis using a combination of deductive and inductive codes.SettingGiven the evidence on industry influences on clinical practice and the importance to the market of oncology drugs, we sought to better understand cancer physicians’ experiences. Practising consultant medical oncologists and clinical haematologists from four Australian states were interviewed over Zoom.Participants16 cancer physicians were interviewed between November 2021 and March 2022, from 37 invited (response rate 43%). Most were medical oncologists (n=12 of 16, 75%) and male (n=9 of 16, 56%).Outcome measuresThe analysis of all interviews was based on grounded theory. Transcripts were coded and then codes formed into themes with supporting quotes. The themes were then placed into categories, used to describe the broad areas into which the themes could be grouped.ResultsSix themes were identified that fell within two broad categories: cancer physicians’views and experiences of interactionsandmanagement of these interactions. Views and experiences included: the transactional nature of relationships, risks of research dependence, ethical challenges and varied attitudes based on interaction type. Management themes included: lack of useful guidance and reduced interactions during the COVID-19 pandemic. These led to an overarching seventh theme, on the desire for a ‘middle road’. Cancer physicians identified the transactional nature of industry relationships and felt uncomfortable with several types of interactions, including those with sales representatives. Most wanted less contact with industry, and the forced separation that occurred with the COVID-19 pandemic was generally welcome.ConclusionsCancer physicians may have difficulty balancing the perceived need to interact with industry in modern cancer care while maintaining distance to minimise conflicts of interest. Further research is needed to assess management strategies in this area.
The Zoom RDL radial access system for neurointervention: An early single-center experience
Authors: Morsi Rami Z , Kothari Sachin A , Thind Sonam , Desai Harsh , Polster Sean P , Goldenberg Fernando , Coleman Elisheva , Brorson James R , Mendelson Scott , Mansour Ali , Prabhakaran Shyam , Kass-Hout Tareq 
Published: May 2023

Background
The transradial approach (TRA) for neurointerventional procedures is increasingly being used given its technical feasibility and safety. However, catheter trackability and device deliverability are reported barriers to TRA adoption.

Methods
This is the first report describing the technical feasibility and performance of using the Zoom RDL Radial Access System (Imperative Care, Inc., Campbell, CA) in 29 patients who underwent neurointerventional procedures from October 2022 to January 2023 in a single-center institution.

Results
Mean age of the study population was 61.9±17.2 years, 79.3% were male (23/29), and 62.1% were black (18/29). The most common procedures were stroke thrombectomy (31.0%, 9/29) and aneurysm embolization (27.6%, 8/29). All the stroke thrombectomy procedures were successfully performed; first-pass effect rate (mTICI≥2 c in one pass) was achieved in 66.7% (6/9) of cases. We used TRA in 86.2% of cases (25/29), including distal radial/snuffbox access in 31.0% (9/29) of cases. The radial diameter was >2 mm for all cases. An intermediate/aspiration catheter was used in 89.7% (26/29) of cases. Access success was achieved in 89.7% of cases (26/29); two cases required conversion from TRA to transfemoral approach (6.9%) and one case required conversion to a different guide catheter (3.4%). There were no access site complications or other Zoom RDL-related complications. One intracerebral hemorrhage, and one procedure-related thrombus were observed.

Conclusions
The use of Zoom RDL Radial Access System is technically feasible and effective for complex neurointerventional procedures with low complication rates.
Red cell haemolysis secondary to intraosseous (IO) blood transfusion in adult patients with major trauma: a systematic review
Authors: Ellington Matt , Walker I , Barnard E 
Published: May 2023

IntroductionIntraosseous (IO) administration of medications and blood products is accepted practice in major trauma when intravenous access is not immediately available. However, there is a concern that the high infusion pressures required for IO transfusion may increase the risk of red cell haemolysis and its associated complications. The aim of this systematic review is to synthesise the existing evidence describing the risks of red cell haemolysis in IO blood transfusion.MethodsWe undertook a systematic search of MEDLINE, CINAHL and EMBASE using the search terms: “intraosseous transfusion” and “haemolysis”. Two authors independently screened abstracts, and reviewed full-text articles against the inclusion criteria. Reference lists of included studies were reviewed and a grey literature search undertaken. Studies were assessed for risk of bias. Inclusion criteria were: all human and animal study types that reported novel data on IO-associated red cell haemolysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was used.ResultsTwenty-three abstracts were identified; n=9 full papers met the inclusion criteria. No further studies were identified from reference lists or grey literature. These papers included: seven large animal translational studies, a prospective and a retrospective human study. The overall risk of bias was high. One animal study with good translatability to adult patients with trauma demonstrated haemolysis. Other animal studies had methodological constraints that limit their human applicability. No haemolysis was observed in low-density flat bones (sternum), whereas haemolysis was reported in long bones (humerus, tibia). IO infusion using a three-way tap was associated with haemolysis. Conversely, pressure bag transfusion was not associated with haemolysis, but this method may result in insufficient flow rates for effective resuscitation.ConclusionsThere is a paucity of high-quality evidence surrounding the risks of red cell haemolysis in IO blood transfusion. However, evidence from one study suggests that the likelihood is increased by use of a three-way tap to administer blood transfusion to young adult male patients with trauma. Further research is needed to address this important clinical question.PROSPERO registration numberCRD42022318902.
Cancer pain assessment and management: does an institutional approach individualise and reduce cost of care?
Authors: Diernberger Katharina , Clausen Eleanor , Murray Gordon , Wee Bee , Kaasa Stein , Hall Peter , Fallon Marie 
Published: May 2023

ObjectivesTo understand individual prescribing and associated costs in patients managed with the Edinburgh Pain Assessment and management Tool (EPAT).MethodsThe EPAT study was a two-arm parallel group cluster randomised (1:1) trial, including 19 UK cancer centres. Study outcome assessments, including pain levels, analgesia and non-pharmacological and anaesthetic interventions, collected at baseline, 3–5 days and, if applicable, 7–10 days after admission. Costs calculated for inpatient length of stay (LoS), medications and complex pain interventions. Analysis accounted for the clustered nature of the trial design. In this post-hoc analysis, healthcare utilisation and costs are presented descriptively.Participants10 centres randomised to EPAT (487 patients) and 9 (449 patients) to usual care (UC).Main outcome measuresPharmacological and non-pharmacological management, complex pain interventions, length of hospital stay and costs related to these outcomes.ResultsThe mean per patient hospital cost was £3866 with EPAT and £4194 with UC, reflecting a mean LoS of 2.9 days and 3.1 days, respectively. Costs were lower for non-opioids, Non-steroidal anti-inflammatories (NSAIDs) and opioids but slightly higher for adjuvants with EPAT than with UC. The mean per-patient opioid costs were £17.90 (EPAT) and £25.80 (UC). Mean per patient costs of all medication were £36 (EPAT) and £40 (UC).Complex pain intervention costs were £117 with EPAT per patient and £90 with UC. Overall mean cost per patient was £4018.3 (95% CI 3698.9 to 4337.8) with EPAT and £4323.8 (95% CI 4060.0 to 4587.7) with UC.ConclusionsEPAT facilitated personalised medicine and may result in less opioids, more specific treatments, improved pain outcomes and cost savings.
Variation in the electronic, mechanical, and structural properties among the polymorphs of bismuth ferrite: a first-principles approach
Authors: Srihari N. V. , Nayak Sanjay , Poornesh P. , Nagaraja K. K. 
Published: May 2023

AbstractBismuth ferrite has been under intense research for many years as it can exhibit first- and second-order transitions where all the phases have distinct properties encapsulating various exciting phenomena. This work reports a computational study of bismuth ferrite and its varied phases using density functional theory with the implementation of Hubbard correction for increased accuracy. The proposed method is validated through Linear Response Theory using Quantum ESPRESSO. The phase transition and the mechanical properties are explored by calculating elastic tensors for different polymorphs. A negative Poisson's ratio for the tetragonal phase supporting its growth in compressive environments is predicted. The electronic properties of different phases of bismuth ferrite are explored, which helps in understanding properties such as charge transfer excitation, metal–insulator transition, ferroelectric nature based on lone pair charges and orbital hybridization. The phonon modes of different phases are also investigated.Graphical abstract
Noncommutativity and physics: a non-technical review
Authors: Chamseddine Ali H. , Connes Alain , van Suijlekom Walter D. 
Published: May 2023

AbstractWe give an overview of the applications of noncommutative geometry to physics. Our focus is entirely on the conceptual ideas, rather than on the underlying technicalities. Starting historically from the Heisenberg relations, we will explain how in general noncommutativity yields a canonical time evolution, while at the same time allowing for the coexistence of discrete and continuous variables. The spectral approach to geometry is then explained to encompass two natural ingredients: the line element and the algebra. The relation between these two is dictated by so-called higher Heisenberg relations, from which both spin geometry and non-abelian gauge theory emerges. Our exposition indicates some of the applications in physics, including Pati–Salam unification beyond the Standard Model, the criticality of dimension 4, second quantization and entropy.
Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma
Authors: Horowitch Brooke , Lee Daniel Y. , Ding Min , Martinez-Morilla Sandra , Aung Thazin Nwe , Ouerghi Feriel , Wang Xueting , Wei Wei , Damsky William , Sznol Mario , Kluger Harriet , Rimm David L. , Ishizuka Jeffrey J. 
Published: May 2023

Abstract

Purpose:
IFN signaling in the tumor microenvironment is a critical determinant of both response and resistance of cancer to immune checkpoint inhibitors (ICI). We hypothesized that distinct patterns of IFN signaling in melanoma are associated with clinical response or resistance to ICIs.

Experimental Design:
Two tissue microarrays containing samples from 97 patients with metastatic melanoma who received nivolumab, pembrolizumab, or a combination of ipilimumab and nivolumab at Yale New Haven Hospital between 2011 and 2017 were randomized into discovery and validation cohorts. Samples were stained and visualized using multiplexed immunofluorescence microscopy for STAT1, STAT1 phosphorylated at Y701 (pSTAT1Y701), and PD-L1, and signals were quantified using the automated quantitative analysis method of quantitative immunofluorescence. Treatment response was assessed using RECIST, and overall survival was analyzed. For in vitro studies, human melanoma cell lines were stimulated with IFNγ and IFNβ, and Western blotting was performed.

Results:
Pretreatment STAT1 levels were higher in responders to ICIs [complete response/partial response/stable disease (SD) for &gt; 6 months] than in nonresponders (SD &lt; 6 months/progressive disease). Higher pretreatment STAT1 levels were associated with improved survival after ICIs in both the discovery and validation cohorts. Western blot analysis of human melanoma cell lines stimulated with IFN demonstrated distinct patterns of upregulation of STAT1 compared with pSTAT1Y701 and PD-L1. When combining STAT1 and PD-L1 markers, patients with STAT1highPD-L1low tumors had improved survival compared with those with STAT1lowPD-L1high tumors.

Conclusions:
STAT1 may better predict melanoma response to ICIs than current strategies, and combined STAT1 and PD-L1 biomarkers may provide insight into IFN-responsive versus IFN-resistant states.
Patient-Reported Outcomes as Interradiographic Predictors of Response in Non–Small Cell Lung Cancer
Authors: Bhatt Ambika S. , Schabath Matthew B. , Hoogland Aasha I. , Jim Heather S.L. , Brady-Nicholls Renee 
Published: May 2023

Abstract

Purpose:
Minimally invasive biomarkers have been used as important indicators of treatment response and progression in cancers such as prostate and ovarian. Unfortunately, all biomarkers are not prognostic in all cancer types and are often not routinely collected. Patient-reported outcomes (PRO) provide a non-obtrusive, personalized measure of a patient's quality of life and symptomatology, reported directly from the patient, and are increasingly collected as part of routine care. Previous literature has shown correlations between specific PROs (i.e., insomnia, fatigue) and overall survival. Although promising, these studies often only consider single time points and ignore patient-specific dynamic changes in individual PROs, which might be early predictors of treatment response or progression.

Experimental Design:
In this study, PRO dynamics were analyzed to determine if they could be used as interradiographic predictors of tumor volume changes among 85 patients with non–small cell lung cancer undergoing immunotherapy. PRO questionnaires and tumor volume scans were completed biweekly and monthly, respectively. Correlation and predictive analysis were conducted to identify specific PROs that could accurately predict patient response.

Results:
Changes in tumor volume over time were significantly correlated with dizziness (P &lt; 0.005), insomnia (P &lt; 0.05), and fatigue (P &lt; 0.05). In addition, cumulative changes in insomnia could predict progressive disease with a 77% accuracy, on average 45 days prior to the next imaging scan.

Conclusions:
This study presents the first time that patient-specific PRO dynamics have been considered to predict how individual patients will respond to treatment. This is an important first step in adapting treatment to improve response rates.