bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancer activation via TCP and HD-ZIP and repression by Dof transcription factors mediate giant cell-specific expression
Authors: Hong Lilan , Rusnak Byron , Ko Clint S , Xu Shouling , He Xi , Qiu Dengying , Kang S Earl , Pruneda-Paz Jose L , Roeder Adrienne H K 
Published: February 2023

Abstract
Proper cell-type identity relies on highly coordinated regulation of gene expression. Regulatory elements such as enhancers can produce cell type-specific expression patterns, but the mechanisms underlying specificity are not well understood. We previously identified an enhancer region capable of driving specific expression in giant cells, which are large, highly endoreduplicated cells in the Arabidopsis thaliana sepal epidermis. In this study, we use the giant cell enhancer as a model to understand the regulatory logic that promotes cell type-specific expression. Our dissection of the enhancer revealed that giant cell specificity is mediated primarily through the combination of two activators and one repressor. HD-ZIP and TCP transcription factors are involved in the activation of expression throughout the epidermis. High expression of HD-ZIP transcription factor genes in giant cells promoted higher expression driven by the enhancer in giant cells. Dof transcription factors repressed the activity of the enhancer such that only giant cells maintained enhancer activity. Thus, our data are consistent with a conceptual model whereby cell type-specific expression emerges from the combined activities of three transcription factor families activating and repressing expression in epidermal cells.
Kiwifruit bZIP transcription factorAcePosF21elicits ascorbic acid biosynthesis during cold stress
Authors: Liu Xiaoying , Bulley Sean M , Varkonyi-Gasic Erika , Zhong Caihong , Li Dawei 
Published: February 2023

AbstractCold stress seriously affects plant development, resulting in heavy agricultural losses. L-ascorbic acid (AsA, vitamin C) is an antioxidant implicated in abiotic stress tolerance and metabolism of reactive oxygen species (ROS). Understanding whether and how cold stress elicits AsA biosynthesis to reduce oxidative damage is important for developing cold-resistant plants. Here, we show that the accumulation of AsA in response to cold stress is a common mechanism conserved across the plant kingdom, from single-cell algae to angiosperms. We identified a basic leucine zipper domain (bZIP) transcription factor (TF) of kiwifruit (Actinidia eriantha Benth.), AcePosF21, which was triggered by cold and is involved in the regulation of kiwifruit AsA biosynthesis and defense responses against cold stress. AcePosF21 interacted with the R2R3-MYB TF AceMYB102 and directly bound to the promoter of the gene encoding GDP-L-galactose phosphorylase 3 (AceGGP3), a key conduit for regulating AsA biosynthesis, to up-regulate AceGGP3 expression and produce more AsA, which neutralized the excess ROS induced by cold stress. On the contrary, VIGS or CRISPR-Cas9-mediated editing of AcePosF21 decreased AsA content and increased the generation of ROS in kiwifruit under cold stress. Taken together, we illustrated a model for the regulatory mechanism of AcePosF21-mediated regulation of AceGGP3 expression and AsA biosynthesis to reduce oxidative damage by cold stress, which provides valuable clues for manipulating the cold resistance of kiwifruit.
Can We have Justified Beliefs about Fundamental Properties?
Authors: Bradley Darren 
Published: February 2023

Abstract
An attractive picture of the world is that some features are metaphysically fundamental and others are derivative, with the derivative features grounded in the fundamental features. But how do we have justified beliefs about which features are fundamental? What is the epistemology of fundamentality? I sketch a response in this paper. The guiding idea is that the same properties cause the same experiences. I argue that a probabilistic connection between epistemic fundamentality and metaphysical fundamentality is sufficient for justified beliefs about the metaphysically fundamental.
Option Return Predictability with Machine Learning and Big Data
Authors: Bali Turan G , Beckmeyer Heiner , Mörke Mathis , Weigert Florian 
Published: February 2023

AbstractDrawing upon more than 12 million observations over the period from 1996 to 2020, we find that allowing for nonlinearities significantly increases the out-of-sample performance of option and stock characteristics in predicting future option returns. The nonlinear machine learning models generate statistically and economically sizable profits in the long-short portfolios of equity options even after accounting for transaction costs. Although option-based characteristics are the most important standalone predictors, stock-based measures offer substantial incremental predictive power when considered alongside option-based characteristics. Finally, we provide compelling evidence that option return predictability is driven by informational frictions and option mispricing.Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Measuring the impact of steroid therapy on health-related quality of life in patients with rheumatic diseases: international development of a glucocorticoid treatment–specific patient-reported outcome measure
Authors: Bridgewater Susan , Shepherd Michael A , Dawson Jill , Richards Pamela , Silverthorne Christine , Ndosi Mwidimi , Almeida Celia , Black Rachel J , Cheah Jonathan T L , Dures Emma , Ghosh Nilasha , Hoon Elizabeth A , Lyne Suellen , Navarro-Millan Iris , Pearce-Fisher Diyu , Ruediger Carlee , Tieu Joanna , Yip Kevin , Mackie Sarah L , Goodman Susan , Hill Catherine , Robson Joanna C 
Published: February 2023

Abstract

Objectives
Glucocorticoids (GCs) (‘steroids’) are used to treat rheumatic diseases but adverse effects are common. We aimed to explore the impact of GC therapy on health-related quality of life (HRQoL), to inform the development of a treatment-specific patient-reported outcome measure (PROM) for use in clinical trials and practice.

Methods
Semi-structured qualitative interviews were conducted with patients from the UK, USA and Australia, treated for a rheumatic condition with GCs in the last 2 years. Purposive sampling was used to select participants with a range of demographic and disease features. An initial conceptual framework informed interview prompts and cues. Interviews elicited GC-related physical and psychological symptoms and salient aspects of HRQoL in relation to GC therapy. Interview data were analysed inductively to develop initial individual themes and domains. Candidate questionnaire items were developed and refined.

Results
Sixty semi-structured qualitative interviews were conducted (UK n = 34, USA n = 10, Australia n = 16). The mean age was 58 years; 39/60 were female; and 18 rheumatic diseases were represented. Some 126 individual themes were identified and organized into six domains: physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation; impact of steroids on relationships; and benefits of steroids. Candidate questionnaire items were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews and linguistic translatability assessment, informing a draft questionnaire.

Conclusion
We describe an international qualitative study to develop candidate items for a treatment-specific PROM for patients with rheumatic diseases. A future survey will enable the validation of a final version of the PROM.
Rapid improvement of systemic sclerosis-associated intestinal pseudo-obstruction with intravenous immunoglobulin administration
Authors: Matsuda Kazuki M , Yoshizaki Ayumi , Kuzumi Ai , Toyama Satoshi , Awaji Kentaro , Miyake Tomomi , Sato Shinichi 
Published: February 2023

Abstract

Objectives
SSc is an autoimmune disease characterized by excessive fibrosis in multiple organs, including the gastrointestinal (GI) tract. GI symptoms of SSc such as intestinal pseudo-obstruction (IPO) are often refractory to conventional intervention and can result in longer in-hospital stay or even increased mortality. We aimed to summarize the insights to date regarding the efficacy of IVIG against GI symptoms of SSc to unveil what we should focus on in future studies.

Methods
Herein we report the response of GI symptoms in three cases with SSc-myositis overlap who received IVIG administration. We also conducted a systematic literature review to summarize previous reports regarding the efficacy of IVIG upon the GI manifestations of SSc, according to the PRISMA 2020 guideline.

Results
The case series demonstrated remarkable and rapid improvement of GI symptoms, including IPO, after IVIG administration. The literature review revealed that previous reports also support the efficacy and safety of IVIG against GI manifestations of SSc. However, they were all retrospective studies and lacking description of the short-term outcome after IVIG administration with objective and quantitative metrics.

Conclusion
IVIG seems to be a promising therapeutic option for the management of GI symptoms in SSc, including IPO. Investigators should focus more on short-term outcomes to properly assess the therapeutic benefit of IVIG, ideally using reliable quantitative measures in a multicentre randomized placebo-controlled setting.
‘A Biological Side Effect’: Yaws Eradication, Syphilis, and Debates over ‘Cross-Immunity’ at the World Health Organization, 1948–1990
Authors: Bowen Elliott 
Published: February 2023

Summary
The World Health Organisation’s (WHO) yaws eradication campaign (1952–64) has been called ‘one of the greatest public health achievements’ of the twentieth century. Yet the campaign was not an unalloyed success. Shortly after its initiation, experts began to wonder if yaws’ disappearance might facilitate the spread of syphilis—whose genetic similarities with yaws had long fuelled speculation that the two treponemal diseases conferred a measure of immunological protection on each other. As the WHO’s work proceeded, evidence for this ‘cross-immunity’ hypothesis steadily accumulated from across the developing world. Though initially receptive to this idea, by the 1970s, WHO officials were increasingly downplaying the idea of cross-immunity, arguing instead that rising rates of syphilis were a product of the era’s ‘sexual revolution’. Animated by racialised discourses of sexual promiscuity, the WHO’s shifting treponemal discourse highlights important continuities between Cold War disease control efforts and the ‘colonial medicine’ of the early twentieth century.
Doctors and Parents in Children’s Wards: Tel-Hashomer Hospital’s Unrestricted Visitations in 1950s’ Israel
Authors: Ayalon Ella , Kirsh Nurit 
Published: February 2023

Summary
In this paper, we explore the acceptance of parents into children’s wards in Tel-Hashomer Hospital, an important foundation of Israel’s health system. In 1953, Tel-Hashomer was the first hospital in Israel to conduct an experimental programme of minimum separation between children and their parents, influenced by the theory of British psychoanalyst and psychiatrist John Bowlby. Tel-Hashomer medical staff encouraged parents to stay long hours near the bedsides of their daughters and sons, which led to a notable change in the ward’s daily routine. Eventually, parents became an inseparable part of the ward. This tendency to embrace and welcome parents into the wards was especially surprising when one considers that many of these parents were of Mizrahi origin and suffered an orientalist, racialised stigma of unfit parenting.
Post‐ovulatory aging is associated with altered patterns for small ubiquitin‐like modifier (SUMO) proteins and SUMO‐specific proteases
Authors: Feitosa Weber Beringui , Morris Patricia L. 
Published: February 2023

AbstractMammalian oocytes are ovulated arrested at metaphase of the second meiotic division. If they are not fertilized within a short period, the oocyte undergoes several progressive morphological, structural, and molecular changes during a process called oocyte aging. Herein, we focused on those functional events associated with proper cytoskeleton organization and those that correlate with spindle displacement and chromosome misalignment or scatter. Post‐translational modifications by Small Ubiquitin‐like Modifier (SUMO) proteins are involved in spindle organization and here we demonstrate that the SUMO pathway is involved in spindle morphology changes and chromosome movements during oocyte aging. SUMO‐2/3 as well as the SUMO‐specific proteases SENP‐2 localization are affected by postovulatory aging in vitro. Consistent with these findings, UBC9 decreases during oocyte aging while differential ubiquitination patterns also correlate with in vitro oocyte aging. These results are consistent with postovulatory aging‐related alterations in the posttranslational modifications of the spindle apparatus by SUMO and its SENP proteases. These findings are suggestive that such age‐related changes in SUMOylation and the deSUMOylation of key target proteins in the spindle apparatus and kinetochore may be involved with spindle and chromosome alignment defects during mammalian oocyte postovulatory aging. Such findings may have implications for ART‐related human oocyte aging in vitro regarding the activities of the SUMO pathway and fertilization success.
Pain and Disability Following Exercise-Induced Injury in Prognostic and Intervention Studies: The Why May Be More Important Than the How
Authors: Bishop Mark D. , George Steven Z. 
Published: February 2023

Objectives:
In preclinical prognostic studies, the description of expected outcomes during an informed consent process indicates that the extent of pain and disability experienced and recovery time is unknown. In intervention studies, the consent process suggests that pain and disability will definitely occur and a treatment provided. Our objective was to determine whether study design (prognosis or intervention) was associated with the severity of pain intensity and disability reports from a preclinical model.

Materials and Methods:
We pooled pain and disability outcomes from prognostic and intervention studies using an exercise-induced muscle injury model of pain. Pain intensity, disability, and fear of pain were collected by validated self-report measures. Pain and disability data were z-transformed for pooled analyses and compared across the study design.

Results:
Data from 310 people were included. The primary findings were that self-reported pain intensity and disability were: (1) higher in prognostic studies than in the intervention studies and (2) associated with fear of pain. A secondary finding was that fear of pain was lower in the intervention compared with the prognostic studies.

Discussion:
Although there are other possible explanations, we speculate that these results could be related to the uncertainty inherent to providing informed consent for a prognostic study. In light of these findings, we recommend that informed consent language be more carefully considered when pain is induced in a controlled manner. Incorporating informed consent language commonly used in prognostic studies could result in higher pain intensity and disability ratings in studies that use preclinical models to test the efficacy of pain interventions.
A Parent-Targeted Group Intervention for Pediatric Pain Delivered In-Person or Virtually
Authors: Lee Soeun , Dick Bruce D. , Jordan Abbie , McMurtry C. Meghan 
Published: February 2023

Objectives:
Parents play integral roles in their youth’s chronic pain and can experience elevated distress related to caregiving. This study examined a cognitive-behavior therapy-based parent-targeted group intervention, including understudied/novel resilience/risk (eg, distress, parenting self-regulation), and compared the effect of in-person versus virtual delivery format.

Hypotheses:
(1) Adequate feasibility and acceptability (enrolment>33%, attendance >60%, attrition <25%, satisfaction ratings >90%), with higher indicators of feasibility in the virtual groups; (2) Significant improvements in parent psychological flexibility, protectiveness, distress, and parenting self-regulation at posttreatment that were maintained at follow-up, with no difference between delivery type.

Methods:
Parents were enroled from an outpatient pediatric chronic pain clinic and participated in the group intervention in-person or virtually; questionnaires were completed at baseline, posttreatment, and 3-month follow-up.

Results:
Enrolment (55% in-person, 65% virtual) and attendance (86% in-person, 93% virtual) were higher, and attrition was lower than expected (4% in-person, 7% virtual). Satisfaction was high (4.95/5 in-person, 4.85/5 virtual); on written feedback, parents enjoyed connecting with other parents (27/56, 48%) the most. The least preferred were the virtual format (5/36, 14%) and timing of the group (6/52, 12%). There were no differences between delivery formats in feasibility/acceptability. The intervention significantly improved parents’ psychological flexibility, protectiveness, distress, and parenting self-regulation over time. A small group difference favored the in-person format for psychological flexibility, and an interaction effect for parenting self-regulation was found.

Discussion:
This standalone parent-targeted group intervention had positive effects on parent outcomes delivered either in-person or virtually.
Which Radiographic Parameter Can Aid in Deciding Optimal Allograft Height for Anterior Cervical Discectomy and Fusion?
Authors: Yang Jae Jun , Park Sehan , Kim Dong-Min 
Published: February 2023

Study Design:
Retrospective cohort study.

Objectives:
To identify preoperative radiographic parameters that can guide optimal allograft height selection for anterior cervical discectomy and fusion (ACDF).

Summary of Background Data:
Allograft height selection for ACDF depends on intraoperative assessment supported by trials; however, there is currently no radiographic reference parameter that could aid in allograft height selection for improved outcomes.

Methods:
A total of 148 patients who underwent ACDF using allografts and were followed up for more than 1 year were retrospectively reviewed. Fusion rates, subsidence, segmental lordosis, and foraminal height were assessed. Segments were divided into 2 groups according to whether the inserted allograft height was within 1 mm from the following 3 reference radiographic parameters: (1) uncinate process height, (2) adjacent disc height, and (3) preoperative disc height +2 mm.

Results:
This study included 101 patients with 163 segments. Segments with an allograft-uncinate height difference of ≤1 mm had a significantly higher fusion rate at 1-year follow-up compared with segments with allograft-uncinate height difference of >1 mm [85/107 (79.4%) vs. 35/56 (62.5%); P=0.025]. Subsidence, segmental lordosis, and foraminal height did not significantly differ between the groups when segments were divided according to uncinate height. Multivariate logistic regression analysis demonstrated that allograft-uncinate height difference of ≤1 mm and allograft failure were factors associated with fusion.

Conclusions:
The uncinate process height can guide optimal allograft height selection for ACDF. Using an allograft with an allograft-uncinate height difference of ≤1 mm resulted in a higher fusion rate. Therefore, the uncinate process height should be checked preoperatively and used in conjunction with intraoperative assessment when selecting allograft height.
U.S. Adult Critical Care Beds Per Capita: A 2021 County-Level Cross-Sectional Study
Authors: Kempker Jordan A. , Stearns Erin , Peterson Emily N. , Waller Lance A. 
Published: February 2023

IMPORTANCE:
Per capita geographic distribution of adult critical care beds can be utilized for healthcare resources assessments.

OBJECTIVES:
Describe the per capita distribution of staffed adult critical care beds across the United States.

DESIGN, SETTING AND PARTICIPANTS:
Cross-sectional epidemiologic assessment of November 2021 hospital data from the Department of Health and Human Services’ Protect Public Data Hub.

MAIN OUTCOMES AND MEASURES:
Staffed adult critical care beds per adult population.

RESULTS:
The percent of hospitals reporting was high and varied by state/territory (median, 98.6% of states’ hospitals reporting; interquartile range [IQR], 97.8–100%). There was a total of 4,846 adult hospitals accounting for 79,876 adult critical care beds in the United States and its territories. Crudely aggregated at the national-level, this calculated to 0.31 adult critical care beds per 1,000 adults. The median crude per capita density of adult critical care beds per 1,000 adults across U.S. counties was 0.00 per 1,000 adults (county, IQR 0.00–0.25; range, 0.00–8.65). Spatially smoothed county-level estimates were obtained using Empirical Bayes and Spatial Empirical Bayes approaches, resulting in an estimated 0.18 adult critical care beds per 1,000 adults (range from both methodological estimates, 0.00–8.20). When compared to counties in the lower quartile of adult critical care bed density, counties in the upper quartile had higher average adult population counts (mean 159,000 vs 32,000 adults per county) and a choropleth map demonstrated high densities of beds in urban centers with low density across rural areas.

CONCLUSIONS AND RELEVANCE:
Among U.S. counties, the density of critical care beds per capita was not uniformly distributed, with high densities concentrated in highly populated urban centers and relative scarcity in rural areas. As it is unknown what defines deficiency and surplus in terms of outcomes and costs, this descriptive report serves as an additional methodological benchmark for hypothesis-driven research in this area.
Early Versus Delayed Coronary Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation—A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Al Lawati Kumait , Forestell Ben , Binbraik Yasser , Sharif Sameer , Ainsworth Craig , Mathew Rebecca , Amin Faizan , Al Fawaz Mohammed , Pinilla-Echeverri Natalia , Belley-Côté Emilie , Welsford Michelle , Rochwerg Bram 
Published: February 2023

OBJECTIVES:
The optimal timing of coronary angiography remains unclear following out-of-hospital cardiac arrest (OHCA) without ST elevation on electrocardiogram. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of early angiography versus delayed angiography following OHCA without ST elevation.

DATA SOURCES:
The databases MEDLINE, PubMed EMBASE, and CINHAL, as well as unpublished sources from inception to March 9, 2022.

STUDY SELECTION:
A systematic search was performed for randomized controlled trials of adult patients after OHCA without ST elevation who were randomized to early as compared to delayed angiography.

DATA EXTRACTION:
Reviewers screened and abstracted data independently and in duplicate. The certainty of evidence was assessed for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. The protocol was preregistered (CRD 42021292228).

DATA SYNTHESIS:
Six trials were included (n = 1,590 patients). Early angiography probably has no effect on mortality (relative risk [RR] 1.04; 95% CI 0.94–1.15; moderate certainty) and may have no effect on survival with good neurologic outcome (RR 0.97; 95% CI 0.87–1.07; low certainty) or ICU length of stay (LOS) (mean difference 0.41 days fewer; 95% CI –1.3 to 0.5 d; low certainty). Early angiography has an uncertain effect on adverse events.

CONCLUSIONS:
In OHCA patients without ST elevation, early angiography probably has no effect on mortality and may have no effect on survival with good neurologic outcome and ICU LOS. Early angiography has an uncertain effect on adverse events.