bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nudix hydrolase 23 post-translationally regulates carotenoid biosynthesis in plants
Authors: Rao Sombir , Cao Hongbo , O’Hanna Franz Joseph , Zhou Xuesong , Lui Andy , Wrightstone Emalee , Fish Tara , Yang Yong , Thannhauser Theodore , Cheng Lailiang , Dudareva Natalia , Li Li 
Published: February 2024

Abstract
Carotenoids are essential for photosynthesis and photoprotection. Plants must evolve multifaceted regulatory mechanisms to control carotenoid biosynthesis. However, the regulatory mechanisms and the regulators conserved among plant species remain elusive. Phytoene synthase (PSY) catalyzes the highly regulated step of carotenogenesis and geranylgeranyl diphosphate synthase (GGPPS) acts as a hub to interact with GGPP-utilizing enzymes for the synthesis of specific downstream isoprenoids. Here, we report a function of Nudix hydrolase 23 (NUDX23), a Nudix domain-containing protein, in post-translational regulation of PSY and GGPPS for carotenoid biosynthesis. NUDX23 expresses highly in Arabidopsis (Arabidopsis thaliana) leaves. Overexpression of NUDX23 significantly increases PSY and GGPPS protein levels and carotenoid production, whereas knockout of NUDX23 dramatically reduces their abundances and carotenoid accumulation in Arabidopsis. NUDX23 regulates carotenoid biosynthesis via direct interactions with PSY and GGPPS in chloroplasts, which enhances PSY and GGPPS protein stability in a large PSY–GGPPS enzyme complex. NUDX23 was found to co-migrate with PSY and GGPPS proteins and to be required for the enzyme complex assembly. Our findings uncover a regulatory mechanism underlying carotenoid biosynthesis in plants and offer promising genetic tools for developing carotenoid-enriched food crops.
Molecular basis and evolutionary drivers of endosperm-based hybridization barriers
Authors: Bente Heinrich , Köhler Claudia 
Published: February 2024

Abstract
The endosperm, a transient seed tissue, plays a pivotal role in supporting embryo growth and germination. This unique feature sets flowering plants apart from gymnosperms, marking an evolutionary innovation in the world of seed-bearing plants. Nevertheless, the importance of the endosperm extends beyond its role in providing nutrients to the developing embryo by acting as a versatile protector, preventing hybridization events between distinct species and between individuals with different ploidy. This phenomenon centers on growth and differentiation of the endosperm and the speed at which both processes unfold. Emerging studies underscore the important role played by type I MADS-box transcription factors, including the paternally expressed gene PHERES1. These factors, along with downstream signaling pathways involving auxin and abscisic acid, are instrumental in regulating endosperm development and, consequently, the establishment of hybridization barriers. Moreover, mutations in various epigenetic regulators mitigate these barriers, unveiling a complex interplay of pathways involved in their formation. In this review, we discuss the molecular underpinnings of endosperm-based hybridization barriers and their evolutionary drivers.
Remnant cholesterol traits and risk of stroke: A multivariable Mendelian randomization study
Authors: Wu Zhiyuan , Jiang Yue , Guo Zheng , Li Pingan , Zheng Yulu , Wang Yutao , Zhang Haiping , Balmer Lois , Li Xingang , Tao Lixin , Zhang Qi , Gao Bo , Guo Xiuhua 
Published: February 2024

Abstract
Observational epidemiological studies have reported a relationship between remnant cholesterol and stroke. However, the results are inconclusive, and causality remains unclear due to confounding or reverse causality. Our objective in this study was to investigate the causal relevance of remnant cholesterol and the risk of stroke and its subtypes using the Mendelian randomization (MR) approach. Genome-wide association studies (GWASs) including 115,082 European individuals (UK Biobank) were used to identify instruments for remnant cholesterol, including intermediate-density lipoprotein (IDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol. Summary-level data for total stroke, intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta-analyses conducted by the MEGASTROKE consortium. Univariable and multivariable MR analyses were performed. The GWAS identified multiple single-nucleotide polymorphisms after clumping for remnant cholesterol (n = 52), IDL cholesterol (n = 62), and VLDL cholesterol (n = 67). Assessed individually using MR, remnant cholesterol (weighted median: odds ratio [OR] 1.32 per 1-SD higher trait; 95% CI: 1.04–1.67; P = 0.024) had effect estimates consistent with a higher risk of LAS-IS, driven by IDL cholesterol (OR 1.32; 95% CI: 1.04–1.68; P = 0.022). In multivariable MR, IDL cholesterol (OR 1.46; 95% CI: 1.10–1.93; P = 0.009) retained a robust effect on LAS-IS after controlling for VLDL cholesterol and high-density lipoprotein cholesterol. The MR analysis did not indicate causal associations between remnant cholesterol and other stroke subtypes. This study suggests that remnant cholesterol is causally associated with the risk of LAS-IS driven by IDL cholesterol.
Predicting capillary vessel network hemodynamics in silico by machine learning
Authors: Ebrahimi Saman , Bagchi Prosenjit 
Published: February 2024

Abstract
Blood velocity and red blood cell (RBC) distribution profiles in a capillary vessel cross-section in the microcirculation are generally complex and do not follow Poiseuille’s parabolic or uniform pattern. Existing imaging techniques used to map large microvascular networks in vivo do not allow a direct measurement of full 3D velocity and RBC concentration profiles, although such information is needed for accurate evaluation of the physiological variables, such as the wall shear stress (WSS) and near-wall cell-free layer (CFL), that play critical roles in blood flow regulation, disease progression, angiogenesis, and hemostasis. Theoretical network flow models, often used for hemodynamic predictions in experimentally acquired images of the microvascular network, cannot provide the full 3D profiles either. In contrast, such information can be readily obtained from high-fidelity computational models that treat blood as a suspension of deformable RBCs. These models, however, are computationally expensive and not feasible for extension to the microvascular network at large spatial scales up to an organ level. To overcome such limitations, here we present machine learning (ML) models that bypass such expensive computations but provide highly accurate and full 3D profiles of the blood velocity, RBC concentration, WSS, and CFL in every vessel in the microvascular network. The ML models, which are based on artificial neural network and convolution-based U-net models, predict hemodynamic quantities that compare very well against the true data but reduce the prediction time by several orders. This study therefore paves the way for ML to make detailed and accurate hemodynamic predictions in spatially large microvascular networks at an organ-scale.
A cell-wall-modifying gene-dependent CLE26 peptide signaling confers drought resistance in Arabidopsis
Authors: Endo Satoshi , Fukuda Hiroo 
Published: February 2024

Abstract
Plants respond to various environmental stimuli in sophisticated ways. Takahashi et al. (2018) revealed that CLAVATA3/EMBRYO SURROUNDING REIGON-related 25 (CLE25) peptide is produced in roots under drought stress and transported to shoots, where it induces abscisic acid biosynthesis, resulting in drought resistance in Arabidopsis. However, the drought-related function of the CLE26 peptide, which has the same amino acid sequence as CLE25 (except for one amino acid substitution), is still unknown. In this study, a phenotypic analysis of Arabidopsis plants under repetitive drought stress treatment indicates that CLE26 is associated with drought stress memory and promotes survival rate at the second dehydration event. Additionally, we find that a loss-of-function mutant of a cell-wall-modifying gene, XYLANASE1 (XYN1), exhibits improved resistance to drought, which is suppressed by the mutation of CLE26. XYN1 is down-regulated in response to drought in wild-type plants. A further analysis shows that the synthetic CLE26 peptide is well transported in both xyn1 and drought-pretreated wild-type plants but not in untreated wild-type plants. These results suggest a novel cell wall function in drought stress memory; short-term dehydration down-regulates XYN1 in xylem cells, leading to probable cell wall modification, which alters CLE26 peptide transport, resulting in drought resistance under subsequent long-term dehydration.
Perspectives on advancing innovation and human flourishing through a network of AI institutes
Authors: Makridis Christos A , Borkowski Andrew A , Alterovitz Gil 
Published: February 2024

Abstract
This paper explores the role of artificial intelligence (AI) and the potential to launch a network of AI institutes within federal agencies for innovation and risk management. After providing background about changes in US economic activity and recent AI policy, we study the barriers to science and technology policy and focus on the challenge of coordination in an increasingly complex and interdependent world and how better coordination is required to manage against AI risks. We introduce the concept of a networked approach to intra-agency AI collaboration, drawing on our experience in the National Artificial Intelligence Institute (NAII) at the US Department of Veterans Affairs. Using the NAII as a case-study, we outline a decentralized approach that allows each agency to contribute and coordinate at a local level and in the areas of greatest strength offer substantial opportunity for driving innovation.
Anxiety Predicts Worse Cardiorespiratory Fitness Outcomes in Cardiac Rehabilitation for Lower Socioeconomic Status Patients
Authors: Middleton William A. , Savage Patrick D. , Khadanga Sherrie , Rengo Jason L. , Ades Philip A. , Gaalema Diann E. 
Published: February 2024

Purpose:
The purpose of this study was to show that patients in cardiac rehabilitation (CR) with lower socioeconomic status (SES) have worse clinical profiles and higher rates of psychiatric difficulties and they have lower cardiorespiratory fitness (CRF) improvements from CR than their counterparts with higher SES. Improvement in CRF during CR predicts better long-term health outcomes. Research suggests that higher anxiety impairs CRF in structured exercise regimes and is overrepresented among patients with lower SES. However, no study has determined whether this relationship holds true in CR.

Methods:
This study is a secondary analysis of a randomized controlled trial to improve CR attendance among patients with lower SES. Anxiety (ASEBA ASR; Achenbach System of Empirically Based Assessment, Adult Self Report) and CRF measures (metabolic equivalent tasks [METspeak]) were collected prior to CR enrollment and 4 mo later. Regression was used to examine the association of anxiety with CRF at 4 mo while controlling for other demographic and clinical characteristics.

Results:
Eight-eight participants were included in the analyses, 31% of whom had clinically significant levels of anxiety (T≥ 63). Higher anxiety significantly predicted lower exit CRF when controlling for baseline CRF, age, sex, qualifying diagnosis, and number of CR sessions attended (β=−.05, P= .04). Patients with clinically significant levels of anxiety could be expected to lose >0.65 METspeak in improvement.

Conclusions:
The results from this study suggest that anxiety, which is overrepresented in populations with lower SES, is associated with less CRF improvement across the duration of CR. The effect size was clinically meaningful and calls for future research on addressing psychological factor in CR.
Radiation Exposure Characteristics among Healthcare Workers: Before and After Japan's Ordinance Revision
Authors: Imakhanova Aiganym , Matsuda Naoki , Takamura Noboru , Oriuchi Noboru , Ito Hiroshi , Awai Kazuo , Kudo Takashi 
Published: February 2024

Abstract
Radioactive materials and ionizing radiation have both medical value and disease risks, necessitating radiation dose measurement and risk reduction strategies. The International Commission on Radiological Protection (ICRP) lowered the lens of the eye exposure limit, leading to Japan's revised “Ionizing Radiation Ordinance.” However, the effects on radiation exposure in medical settings and compliance feasibility remain unclear. To examine the impact of the revision to the “Ionizing Radiation Ordinance” and use it for measures to reduce exposure to radiation, a comprehensive analysis was conducted on data collected from Nagasaki University Hospital, Hiroshima University Hospital, and Fukushima Medical University Hospital in 2018, 2020, and April to September 2021. This included information on age, sex, occupation, department, and monthly radiation doses of workers, aiming to assess the impact of the revision to the “Ionizing Radiation Ordinance” on radiation exposure before and after its enforcement. Out of 9,076 cases studied, 7,963 (87.7%) had radiation doses below the measurable limit throughout the year. Only 292 cases (3.2%) exceeded 1 mSv y−1, with 9 doctors and 2 radiological technologists surpassing 5 mSv y−1. Radiological technologists showed significantly higher doses compared to doctors, dentists, and nurses (p < 0.01), while male subjects had significantly higher exposure doses than females (p < 0.01). No significant changes in radiation exposure were observed before and after the revision of the Ionizing Radiation Ordinance; however, variations in radiation exposure control were noted, particularly among nurses and radiological technologists, suggesting the impact of the revision and the need for tailored countermeasures to reduce radiation dose in each group.
Comparison of Scheimpflug and Anterior Segment Optical Coherence Tomography Imaging Parameters for Japanese Patients With Fuchs Endothelial Corneal Dystrophy With and Without TCF4 Repeat Expansions
Authors: Maeno Sayo , Oie Yoshinori , Koto Ryota , Nishida Nozomi , Yamashita Arisa , Yoshioka Michika , Kai Chifune , Soma Takeshi , Koh Shizuka , Yoshihara Masahito , Kawasaki Ryo , Jhanji Vishal , Nakamori Masayuki , Tsujikawa Motokazu , Nishida Kohji 
Published: February 2024

Purpose:
The aim of this study was to investigate the association between cytosine–thymine–guanine trinucleotide repeat (TNR) expansion in TCF4 and the clinical phenotypes of corneal densitometry or anterior segment morphology in Fuchs endothelial corneal dystrophy.

Methods:
This retrospective cross-sectional study included 150 eyes from 75 Japanese consecutive patients with Fuchs endothelial corneal dystrophy. Cytosine–thymine–guanine repeat expansion of leukocyte-derived genomic DNA was analyzed through fragment analysis using polymerase chain reaction and triplet repeat primed polymerase chain reaction. Scheimpflug-based densitometry and anterior segment optical coherence tomography were applied. Corneal densitometry, and corneal and anterior segment morphology parameters were compared between patients with and without TNR expansion of 50 or more (expansion and nonexpansion groups, respectively) using a mixed model.

Results:
The average age of the patients was 66.8 ± 13.0 years, and the modified Krachmer grading scale was 1, 2, 3, 4, 5, and 6 for 7, 32, 28, 51, 6, and 18 eyes, respectively. Sixteen patients (21%) exhibited ≥50 TNR expansion. No significant differences in sex, age, history of keratoplasty, modified Krachmer grade, and corneal densitometry in either diameter or depth were observed between the 2 groups. No significant differences in anterior segment morphology, including the anterior chamber depth and anterior chamber angle width parameters, were observed using a univariate mixed model, except for central corneal thickness (P = 0.047). However, according to the multivariate mixed model, repeat expansion was not significantly associated with central corneal thickness (P = 0.27).

Conclusions:
No significant differences in clinical phenotypes were found between Japanese patients having Fuchs endothelial corneal dystrophy with and without TNR expansion.
Unilateral Granular Type 2 Corneal Dystrophy With Exacerbation After LASIK
Authors: Bostan Cristina , Randleman J. Bradley 
Published: February 2024

Purpose:
The aim of this study was to report a case of unilateral granular corneal dystrophy type 2 (GCD2) with exacerbation after bilateral laser in situ keratomileusis (LASIK).

Methods:
Clinical evaluation, Scheimpflug imaging, anterior segment optical coherence tomography (AS-OCT), cytology, and genetic testing were used to confirm the diagnosis of unilateral GCD2 with exacerbation after bilateral LASIK. Detailed literature review for possible unilateral GCD2 presentations was performed.

Results:
A 54-year-old White woman presented with blurred vision in her left eye and a history of bilateral LASIK performed 8 years before. Examination revealed dense opacities in the left cornea only, which were confirmed to be confined to the LASIK interface and adjacent corneal stromal tissue, as determined by AS-OCT. The patient underwent flap lift, interface debris removal, and stromal bed phototherapeutic keratectomy. Cytological analysis showed eosinophilic corneal stromal deposits that stained with trichrome stain and were congophilic on Congo red stain. Genetic testing was positive for heterozygous GCD2 transforming growth factor β–induced gene (TGFBI), c.371G>A, p.R124H mutation. There were no opacities identifiable in the right eye on serial slit-lamp examination, Scheimpflug imaging, or OCT imaging at 4 or 8 years after bilateral LASIK. Literature review failed to identify any previous reports of unilateral GCD2.

Conclusions:
This is the first known reported case of unilateral granular corneal dystrophy type 2. LASIK is contraindicated in eyes with corneal stromal dystrophies related to mutations in TGFBI as both flap creation and laser ablation can exacerbate visually significant opacity formation. Scheimpflug and AS-OCT imaging are useful to identify opacities in GCD2.
Self-Chiropractic Cervical Spinal Manipulation Resulting in Fatal Vertebral Artery Dissection
Authors: Fink Cameron , Bryce Clare H. , Knight Laura D. 
Published: February 2024

Abstract
Chiropractic cervical spinal manipulations have several complications and can result in vascular injury, including traumatic dissection of the vertebral arteries. A 43-year-old woman was admitted to the emergency department after performing a self-chiropractic spinal manipulation. She experienced headache and vomiting and was unresponsive with severe hypertension at the time of hospital admission. Clinical computerized tomography angiography showed narrowing of the right vertebral artery but was inconclusive for dissection or thrombosis. At autopsy, subacute dissection of the right vertebral artery was identified along with cerebral edema and herniation. A small peripheral pulmonary thromboembolism in the right lung was also seen. Neuropathology consultation confirmed the presence of diffuse cerebral edema and acute hypoxic-ischemic changes, with multifocal acute subarachnoid and intraparenchymal hemorrhage of the brain and spinal cord. This case presents a unique circumstance of a fatal vertebral artery dissection after self-chiropractic manipulation that, to the best of our knowledge, has not been previously described in the medical literature.
Th-Cell Subsets of Submandibular Lymph Nodes in Peri-Implantitis
Authors: Zhang Hongming , Sun Mengzhe , Xu Haisong , Huang Hui 
Published: February 2024

Background:
Implant surgery is a popular operation in craniomaxillofacial surgery, but the occurrence of peri-implantitis affects the success and survival rate of the implant. Research has found that Th-cell–related cytokines are associated with peri-implantitis. However, the distribution and proportions of Th-cell subsets in submandibular lymph nodes’ immune environments during the progression of peri-implantitis remain unclear.

Methods:
Forty-eight rats were randomly divided into 4 groups: the control group, the 1-week ligation peri-implantitis induction (Lig 1w) group, the Lig 2w group, and the Lig 4w group (n=12). Ligation was maintained for different times to induce peri-implantitis 4 weeks after implantation. Inflammation and bone resorption were examined by clinical probing and micro-CT. The submandibular lymph nodes were harvested for quantitative real-time polymerase chain reaction and flow cytometry to obtain the Th-cell profiles.

Results:
With increasing ligation time, more redness and swelling in the gingiva and more bone resorption around the implant were observed (P<0.05). The proportions of Th1 and Th17 cells increased, the proportion of Th2 cells decreased, and the proportion of Treg cells first increased and then decreased in the lymph nodes (P<0.05).

Conclusions:
This study provided a preliminary characterization of the temporal distribution of Th cells in lymph nodes of peri-implantitis. Persistent elevation of Th1 and Th17 proportions and decrease of Treg proportion may be the cause of bone resorption in peri-implantitis. Lymphatic drainage may be a bridge between craniomaxillofacial diseases and systemic diseases. Early immune support against T cells may be a potential therapeutic idea for the prevention of implant failure and the potential risk of systemic disease.
Primary Failure of Dental Eruption Due to Variants Parathyroid Hormone Receptor 1: Retrospective Study and Proposal of Guidelines Treatment
Authors: Thuaire Antoine , Delebarre Hélène , Marsili Luisa , Colson Cindy , Vanlerberghe Clemence , Lauwers Ludovic , Raoul Gwenael , Touzet-Roumazeille Sandrine , Ferri Joël 
Published: February 2024

Objective:
Primary failure of eruption is characterized by a nonsyndromic defect in tooth eruption in the absence of mechanical obstruction. It is correlated to rare heterozygous variants in the parathyroid hormone receptor 1 gene. The management of primary failure of eruption is complex because many therapies are ineffective. The present study aimed to compare the clinical outcomes of our patients with the findings reported in the literature, and to propose a treatment guideline based on the literature and our experience.

Methods:
Retrospective study of patients affected by primary dental eruption failure in the department and analyse of the results and compare with those of the litterature.

Results:
Twelve patients belonging to 5 families (9 males, 3 females; 13–52 y old) diagnosed and treated in the maxillofacial surgery and stomatology department of the Lille University Hospital were included. All patients showed posterior tooth involvement, and most patients showed bilateral defects. None of the affected teeth had coronal alveolar bone, whereas 6 patients showed root resorption in the affected teeth. Genetic analyses, performed on 11 patients, identified a parathyroid hormone receptor 1 disease-causing variant in 7 of them (63%). Multidisciplinary treatment was required to rehabilitate these patients. Orthodontic interventions, even at an early age, are difficult in affected teeth, which are often blocked or have internal resorption. Moreover, retention of these affected teeth during growth leads to dentoskeletal malocclusions, requiring difficult surgical management in the long term. Therefore, early extraction of these teeth is frequently recommended once the diagnosis has been confirmed. An implant-borne prosthetic rehabilitation can then be achieved at the end of growth after correction of the jaw discrepancy. In case of a late diagnosis, other surgical or noninvasive techniques may be used depending on the clinical situation. Distraction osteogenesis or segmental osteotomy could be discussed for patients with mild phenotypes.

Conclusions:
Early diagnosis of primary eruption defects is crucial to offer appropriate management as early as possible, and so to avoid late complicated treatments.