bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal expression of CUX1 influences autophagy activation in paroxysmal nocturnal hemoglobinuria
Authors: Wu Junshu , Li Liyan , Liu Zhaoyun , Wang Honglei , Chen Yingying , Zeng Lijie , Wang Guanrou , Liu Hui , Fu Rong 
Published: February 2024

Abstract
The mechanism underlying autophagy in paroxysmal nocturnal hemoglobinuria (PNH) remains largely unknown. We previously sequenced the entire genome exon of the CD59– cells from 13 patients with PNH and found genes such as CUX1 encoding Cut-like homeobox 1. Peripheral blood samples from 9 patients with PNH and 7 healthy control subjects were obtained to measure CUX1 expression. The correlation between CUX1 messenger RNA expression and PNH clinical indicators was analyzed. To simulate CUX1 expression in patients with PNH, we generated a panel of PNH cell lines by knocking out PIGA in K562 cell lines and transfected lentivirus with CUX1. CCK-8 and EDU assay assessed cell proliferation. Western blotting was used to detect Beclin-1, LC3A, LC3B, ULK1, PI3K, AKT, p-AKT, mTOR, and p-mTOR protein levels. Autophagosomes were observed with transmission electron microscopy. Chloroquine was used to observe CUX1 expression in PNH after autophagy inhibition. Leukocytes from patients with PNH had lower levels of CUX1 messenger RNA expression and protein content than healthy control subjects. The lactose dehydrogenase level and the percentage of PNH clones were negatively correlated with CUX1 relative expression. We reduced CUX1 expression in a PIGA knockout K562 cell line, leading to increased cell proliferation. Levels of autophagy markers Beclin-1, LC3B, LC3A, and ULK1 increased, and autophagosomes increased. Furthermore, PI3K/AKT/mTOR protein phosphorylation levels were lower. CUX1 expression did not change and cell proliferation decreased in CUX1 knocked down PNH cells after inhibition of autophagy by chloroquine. In brief, CUX1 loss-of-function mutation resulted in stronger autophagy in PNH.
Methods for assembling complex mitochondrial genomes in land plants
Authors: Štorchová Helena , Krüger Manuela 
Published: February 2024

Abstract
The large size and complex structural rearrangements inherent in the mitochondrial genomes of land plants pose challenges for their sequencing. Originally, the assembly of these genomes required the cloning of mitochondrial DNA fragments followed by Sanger sequencing. Subsequently, the advent of next-generation sequencing significantly expedited the process. This review highlights examples of plant mitochondrial genome assembly employing various technologies, including 454 sequencing, Illumina short sequencing reads, and Pacific Biosciences or Oxford Nanopore Technology long sequencing reads. The combination of short and long reads in hybrid assembly has proven to be the most efficient approach for achieving reliable assemblies of land plant mitochondrial genomes.
Ethical challenges of using trial transcripts for research purposes: A case study of the International Criminal Tribunal for the Former Yugoslavia
Authors: Veličković Marina 
Published: February 2024

Abstract
Drawing on three years of empirical research, the article explores four ethical challenges of working with trial transcripts: lack of participant consent; impossibility of research reciprocity; the risk that one’s use of these materials can be harmful to the local communities, and the risk that this use might be harmful to the researchers themselves.
A simple method for estimating time-irreversible nucleotide substitution rates in the SARS-CoV-2 genome
Authors: Misawa Kazuharu , Ootsuki Ryo 
Published: February 2024

Abstract
SARS-CoV-2 is the cause of the current worldwide pandemic of severe acute respiratory syndrome. The change of nucleotide composition of the SARS-CoV-2 genome is crucial for understanding the spread and transmission dynamics of the virus because viral nucleotide sequences are essential in identifying viral strains. Recent studies have shown that cytosine (C) to uracil (U) substitutions are overrepresented in SARS-CoV-2 genome sequences. These asymmetric substitutions between C and U indicate that traditional time-reversible substitution models cannot be applied to the evolution of SARS-CoV-2 sequences. Thus, we develop a new time-irreversible model of nucleotide substitutions to estimate the substitution rates in SARS-CoV-2 genomes. We investigated the number of nucleotide substitutions among the 7862 genomic sequences of SARS-CoV-2 registered in the Global Initiative on Sharing All Influenza Data (GISAID) that have been sampled from all over the world. Using the new method, the substitution rates in SARS-CoV-2 genomes were estimated. The C-to-U substitution rates of SARS-CoV-2 were estimated to be 1.95 × 10−3 ± 4.88 × 10−4 per site per year, compared with 1.48 × 10−4 ± 7.42 × 10−5 per site per year for all other types of substitutions.
Conserved transcription factors NRZ1 and NRM1 regulate NLR receptor-mediated immunity
Authors: Zhang Qingling , Wang Jubin , Li Yuanyuan , Tung Jeffrey , Deng Yingtian , Baker Barbara , Dinesh-Kumar Savithramma P , Li Feng 
Published: February 2024

Abstract
Plant innate immunity mediated by the nucleotide-binding leucine-rich repeat (NLR) class of immune receptors plays an important role in defense against various pathogens. Although key biochemical events involving NLR activation and signaling have been recently uncovered, we know very little about the transcriptional regulation of NLRs and their downstream signaling components. Here, we show that the Toll-Interleukin 1 receptor homology domain containing NLR (TNL) gene N (Necrosis), which confers resistance to Tobacco mosaic virus, is transcriptionally induced upon immune activation. We identified two conserved transcription factors, N required C3H zinc finger 1 (NRZ1) and N required MYB-like transcription factor 1 (NRM1), that activate N in an immune responsive manner. Genetic analyses indicated that NRZ1 and NRM1 positively regulate coiled-coil domain-containing NLR- and TNL-mediated immunity and function independently of the signaling component Enhanced Disease Susceptibility 1. Furthermore, NRZ1 functions upstream of NRM1 in cell death signaling, and their gene overexpression induces ectopic cell death and expression of NLR signaling components. Our findings uncovered a conserved transcriptional regulatory network that is central to NLR-mediated cell death and immune signaling in plants.
Actors, alterations, and authorities: three observations of global policy and its transnational administration
Authors: Moloney Kim , Legrand Tim 
Published: February 2024

Abstract
This Special Issue and its seven contributions seek to shift the gaze of public policy scholarship toward the authorities, legitimacies, and influences of transnational actors on the creation and implementation of global policy and its transnational administration. It is, in large part, both a demonstration of the analytical and explanatory value of accounting for the influence of non-state actors on global issues as well as a normative reflection on what this means for already tenuous connections between publics and those that make decisions on their behalf in global forums. This Issue breaks with heterodox public policy approaches that center on the capabilities of states and international organizations to determine and to deliver global public policy and outcomes. Instead, we widen our gaze to capture the influence of transnational actors such as global commissions, transnational public–private partnerships, philanthropic foundations, non-government organization networks, domestic associations with global influence, quasi-judicial authorities, and global citizen activists. The articles discuss the impact of transnational actors on the policy and administrative spaces of global actors and states alike. By dispensing with the notion that the state and state-created international organizations are the primary locus for public policy and public administration scholarship, the included papers conclude with the implications for scholarship on transnational actor authorities and legitimacies.
Human extracellular matrix (ECM)-like collagen and its bioactivity
Authors: Zhou Hui , Li Wenwei , Pan Lixin , Zhu Tianci , Zhou Teng , Xiao E , Wei Qiang 
Published: February 2024

Abstract
Collagen, the most abundant structural protein in the human extracellular matrix (ECM), provides essential support for tissues and guides tissue development. Despite its widespread use in tissue engineering, there remains uncertainty regarding the optimal selection of collagen sources. Animal-derived sources pose challenges such as immunogenicity, while the recombinant system is hindered by diminished bioactivity. In this study, we hypothesized that human ECM-like collagen (hCol) could offer an alternative for tissue engineering. In this study, a facile platform was provided for generating hCol derived from mesenchymal stem cells with a hierarchical structure and biochemical properties resembling native collagen. Our results further demonstrated that hCol could facilitate basal biological behaviors of human adipose-derived stem cells, including viability, proliferation, migration and adipocyte-like phenotype. Additionally, it could promote cutaneous wound closure. Due to its high similarity to native collagen and good bioactivity, hCol holds promise as a prospective candidate for in vitro and in vivo applications in tissue engineering.
MRVAS—introducing a standardized magnetic resonance scoring system for assessing the extent of inflammatory burden in giant cell arteritis
Authors: Froehlich Matthias , Guggenberger Konstanze V , Vogt Marius , Mihatsch Patrick W , Dalla Torre Giulia , Werner Rudolf A , Gernert Michael , Strunz Patrick P , Portegys Jan , Weng Andreas M , Schmalzing Marc , Bley Thorsten A 
Published: February 2024

Abstract

Objectives
Our aim was to introduce a standardized system for assessing the extent of GCA on MRI, i.e. the Magnetic Resonance Vasculitis Activity Score (MRVAS). To obtain a comprehensive view, we used an extensive MRI protocol including cranial vessels and the aorta with its branches. To test reliability, MRI was assessed by four readers with different levels of experience.

Methods
A total of 80 patients with suspected GCA underwent MRI of the cranial arteries and the aorta and its branches (20 vessel segments). Every vessel was rated dichotomous [inflamed (coded as 1) or not (coded as 0)], providing a summed score of 0–20. Blinded readers [two experienced radiologists (ExR) and two inexperienced radiologists (InR)] applied the MRVAS on an individual vessel and an overall level (defined as the highest score of any of the individual vessel scores). To determine interrater agreement, Cohen’s κ was calculated for pairwise comparison of each reader for individual vessel segments. Intraclass correlation coefficients (ICCs) were used for the MRVAS.

Results
Concordance rates were excellent for both subcohorts on an individual vessel-based (GCA: ICC 0.95; non-GCA: ICC 0.96) and overall MRVAS level (GCA: ICC 0.96; non-GCA: ICC 1.0). Interrater agreement yielded significant concordance (P &lt; 0.001) for all pairs (κ range 0.78–0.98). No significant differences between ExRs and InRs were observed (P = 0.38).

Conclusion
The proposed MRVAS allows standardized scoring of inflammation in GCA and achieved high agreement rates in a prospective setting.
Nonlinear Effect of Preexisting Cranial Adjacent Disc Degeneration on Cumulative 12-Year Revision Risk Following Lumbar Fusions
Authors: Toivonen Leevi A. , Mäntymäki Heikki , Benneker Lorin M. , Kautiainen Hannu , Häkkinen Arja , Neva Marko H. 
Published: February 2024

Study Design.
Retrospective analysis of prospectively collected data.

Objective.
To evaluate how preexisting adjacent segment degeneration status impacts revision risk for adjacent segment disease (ASD) after lumbar fusions.

Summary of Background Data.
ASD incurs late reoperations after lumbar fusion surgeries. ASD pathogenesis is multifactorial. Preexisting adjacent segment degeneration, measured by Pfirrmann, is suggested as one of the predisposing factors. We sought to find deeper insights into this association by using a more granular degeneration measure, the combined imaging score (CIS).

Patients and Methods.
A total of 197 consecutive lumbar fusions for degenerative pathologies were enrolled in a prospective follow-up (median: 12 yr). Preoperative cranial adjacent segment degeneration status was determined using Pfirrmann and CIS, which utilize both radiographs and magnetic resonance imaging. On the basis of CIS, patients were trichotomized into tertiles (CIS <7, CIS 7–10, and CIS >10). The cumulative ASD revision risk was determined for each tertile. After adjusting for age, sex, body mass index, sacral fixation, and fusion length, hazard ratios (95% CI) for ASD revisions were determined for each Pfirrmann and CIS score.

Results.
Patients in the intermediate CIS tertile had a cumulative ASD revision risk of 25.4% (17.0%–37.0%), while both milder degeneration (CIS <7) [13.2% (6.5%–25.8%)] and end-stage degeneration (CIS >10) [13.6% (7.0%–25.5%)] appeared to be protective against surgical ASD. Pfirrmann failed to show a significant association with ASD revision risk. Adjusted analysis of CIS suggested increased ASD revisions after CIS 7, which turned contrariwise after CIS 10.

Conclusions.
The effect of preexisting adjacent segment degeneration on ASD reoperation risk is not linear. The risk appears to increase with advancing degeneration but diminishes with end-stage degeneration. Therefore, end-stage degenerative segments may be considered to be excluded from fusion constructs.

Level of Evidence.
Therapeutic 3.
Ocular Surface Analysis of Dry Eye Disease After Cataract Surgery
Authors: Tangpagasit Wimolwan , Srivanich Onnicha 
Published: February 2024

Purpose:We aimed to compare the efficacy and safety of 0.3% hydroxypropyl methylcellulose/dextran (HPMC/Dextran) and 0.3% sodium hyaluronate (SH) in the treatment of dry eye disease (DED) in postcataract surgery patients by analyzing the presurgery and postsurgery ocular surface.Methods:This double-blinded, randomized, parallel-group study enrolled 96 patients with ocular surface dysfunction, specifically DED, after phacoemulsification. Patients were randomized to receive either HPMC/Dextran (n = 56) or 0.3% SH (n = 40). All patients received 1 drop per eye, 4 times per day. Data from OCULUS Keratograph 5M and Schirmer I tests without anesthesia were collected at baseline and 1 week, 1 month, and 3 months postoperatively.Results:Three months postsurgery, the ocular surface, Schirmer I test, tear meniscus height (TMH), noninvasive tear film break-up time (NITBUT), meibography, redness, and Ocular Surface Disease Index were significantly improved. The Schirmer I test, TMH, and NITBUT improved significantly (P= 0.07, 0.17, and 0.43, respectively; analysis of variance,P< 0.05) in the SH group compared with the HPMC/Dextran group. In a subgroup analysis of patients with severe dry eye, Schirmer I test ≤ 5 mm/5 minutes and NITBUT < 5 significantly improved (P= 0.00 and 0.001, respectively) at 3 months in the SH group compared with the HPMC/Dextran group. Thus, 0.3% SH gave significantly superior tear secretion and tear film instability outcomes.Conclusions:Both types of preservative-free artificial tears are effective in treating postsurgery DED. Compared with HPMC/Dextran, 0.3% SH artificial tears showed more improvements in Schirmer I test and NITBUT postsurgery.
Study of IL-17 and Intercellular Adhesion Molecule-1 in Conjunctivochalasis Using Correlation Analysis
Authors: Ma Kai , Zhou Huanming , Zhang Wei , Liu Jiang , Sha Yongyi , Kong Xueqing , Ni Zhenhua , Xiang Minhong 
Published: February 2024

Purpose:
The aim of this study was to observe the expression of interleukin (IL)-17 and intercellular adhesion molecule (ICAM)-1 in conjunctivochalasis (CCH) and to analyze the correlations between cytokines and the severity of CCH.

Methods:
Serum samples were collected from 22 patients with CCH and 18 normal controls (NCs). The Ocular Surface Disease Index, tear film break-up time, Schirmer I test, and corneal fluorescein staining were used to evaluate the ocular surface signs and symptoms. The concentrations of IL-17, IL-23, and ICAM-1 in serum and cellular supernatants were measured by enzyme-linked immunosorbent assays, and the gene expression levels of cytokines were measured by a quantitative real-time polymerase chain reaction. The relationships between serum concentrations of IL-17, IL-23, and ICAM-1 with clinical ocular surface parameters in CCH were analyzed using the Spearman correlation analysis.

Results:
The concentrations of IL-17 and ICAM-1 in serum and cellular supernatants of CCH were significantly higher than those of NCs (all P < 0.001). The concentrations of IL-23 in serum and cellular supernatants of CCH showed no significant difference from those of NCs (P > 0.05). The mRNA expression levels of IL-17 and ICAM-1 in conjunctival fibroblasts of CCH were significantly higher than those of NCs (all P < 0.001). The mRNA expression of IL-23 in conjunctival fibroblasts of CCH was higher than that of NCs, without a significant difference (P > 0.05). Furthermore, the serum concentrations of IL-17 and ICAM-1 were positively correlated with Ocular Surface Disease Index and fluorescein staining (all P < 0.05), and negatively correlated with break-up time and Schirmer I test of CCH (all P < 0.05).

Conclusions:
The expression levels of IL-17 and ICAM-1 were significantly increased in CCH serum and associated with the disease severity. We postulate that IL-17 and ICAM-1 may play a role in the pathogenesis of CCH. IL-17 and ICAM-1 antagonists may be a potential treatment option for CCH in the future.
Hyperopic LASIK and postoperative corneal steepness: revisiting the 49-diopter limit
Authors: Sella Ruti , Sorkin Nir , Safir Margarita , Beylin Yonatan , Sela Tzahi , Munzer Gur , Kaiserman Igor , Mimouni Michael 
Published: February 2024

Purpose:
To compare corrected distance visual acuity (CDVA) outcomes of hyperopic laser in situ keratomileusis (LASIK) with a postoperative corneal steepness above vs below 49 diopters (D).

Setting:
Care-Vision Laser Centers, Tel-Aviv, Israel.

Design:
Retrospective study.

Methods:
This study included consecutive patients who underwent hyperopic LASIK between January 2013 and December 2019. Hyperopic patients were divided into 2 groups based on postoperative corneal steepness with steep corneas defined >49.0 D and the control group ≤49.0 D. Adjustments were performed to account for differences in baseline and intraoperative parameters.

Results:
Overall, 1703 eyes of 1703 patients were included. Mean age was 48.3 ± 10.0 years, and 45.3% were male. Preoperatively, the steep group (2.4%, n = 41/1703) had steeper mean (44.6 D vs 43.1 D, P < .001) and steep (45.1 D vs 43.5 D, P < .001) keratometry, worse logMAR CDVA (0.07 vs 0.04, P = .02), and higher sphere (4.9 D vs 2.9 D, P < .001). Intraoperatively, they had a higher spherical treatment (4.6 D vs 2.8 D, P < .001). After hyperopic LASIK, the steep group had worse logMAR CDVA (0.10 vs 0.06, P = .01). However, after accounting for differences in baseline and spherical treatment, no significant differences were found in postoperative logMAR CDVA (0.06 vs 0.06, P = .99). The factors that remained associated with worse postoperative CDVA were higher spherical treatment (0.01 logMAR per 1 D, P < .001) and preoperative CDVA (0.60 logMAR per 1.00 logMAR, P < .001).

Conclusions:
Postoperative corneal steepness greater than 49 D is not associated with worse visual outcomes after hyperopic LASIK. However, lower preoperative visual potential and higher spherical treatment applied are associated with worse outcomes. The 49 D cutoff should be revisited.
Caregivers' Contributions to Heart Failure Self-care
Authors: Buck Harleah G. , Howland Chelsea , Stawnychy Michael A. , Aldossary Heba , Cortés Yamnia I. , DeBerg Jennifer , Durante Angela , Graven Lucinda J. , Irani Elliane , Jaboob Saida , Massouh Angela , Oberfrank Natany Da Costa Ferreira , Saylor Martha Abshire , Wion Rachel K. , Bidwell Julie T. 
Published: February 2024

Background
A previous systematic review reporting the contributions of informal, unpaid caregivers to patient heart failure (HF) self-care requires updating to better inform research, practice, and policy.

Objective
The aim of this study was to provide an updated review answering the questions: (1) What specific activities do informal caregivers of adults with HF take part in related to HF self-care? (2) Have the activities that informal caregivers of adults with HF take part in related to HF self-care changed over time? (3) What are the gaps in the science?

Methods
This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, CINAHL, EMBASE, and Cochrane CENTRAL databases were searched. Eligible studies involved an informal, unpaid caregiver of an adult with HF as a study variable or participant. Caregiving activities were benchmarked using the theory of self-care in chronic illness.

Results
Two thousand one hundred fifty-four research reports were identified, of which 64 met criteria. Caregivers' contributions occurred in self-care maintenance (91%), monitoring (54%), and management (46%). Activities performed directly on or to the patient were reported more frequently than activities performed for the patient. Change over time involved the 3 domains differentially. Gaps include ambiguous self-care activity descriptions, inadequate caregiving time quantification, and underrepresented self-care monitoring, supportive, and communication activities.

Conclusions
Newly identified caregiver-reported activities support updating the theory of self-care in chronic illness to include activities currently considered ancillary to HF self-care. Identified gaps highlight the need to define specific caregiving activities, determine task difficulty and burden, and identify caregiver self-care strategy and education needs. Exposing the hidden work of caregiving is essential to inform policy and practice.