bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SmMYB36-SmERF6/SmERF115 module regulates the biosynthesis of tanshinones and phenolic acids in salvia miltiorrhiza hairy roots
Authors: Li Qi , Fang Xin , Zhao Ying , Cao Ruizhi , Dong Juane , Ma Pengda 
Published: October 2022

Abstract
Tanshinone and phenolic acids are the most important active substances of Salvia miltiorrhiza, and the insight into their transcriptional regulatory mechanisms is an essential process to increase their content in vivo. SmMYB36 has been found to have important regulatory functions in the synthesis of tanshinone and phenolic acid; paradoxically, its mechanism of action in S. miltiorrhiza is not clear. Here, we demonstrated that SmMYB36 functions as a promoter of tanshinones accumulation and a suppressor of phenolic acids through the generation of SmMYB36 overexpressed and chimeric SmMYB36-SRDX (EAR repressive domain) repressor hairy roots in combination with transcriptomic-metabolomic analysis. SmMYB36 directly down-regulate the key enzyme gene of primary metabolism, SmGAPC, up-regulate the tanshinones biosynthesis branch genes SmDXS2, SmGGPPS1, SmCPS1 and down-regulate the phenolic acids biosynthesis branch enzyme gene, SmRAS. Meanwhile, SmERF6, a positive regulator of tanshinone synthesis activating SmCPS1, was up-regulated and SmERF115, a positive regulator of phenolic acid biosynthesis activating SmRAS, was down-regulated. Furthermore, the seven acidic amino acids at the C-terminus of SmMYB36 are required for both self-activating domain and activation of target gene expression. As a consequence, this study contributes to reveal the potential relevance of transcription factors synergistically regulating the biosynthesis of tanshinone and phenolic acid.
DNA-free genome editing in grapevine using CRISPR/Cas9 ribonucleoprotein complexes followed by protoplast regeneration
Authors: Najafi Samaneh , Bertini Edoardo , D’Incà Erica , Fasoli Marianna , Zenoni Sara 
Published: October 2022

AbstractCRISPR/Cas9 genome editing technology can overcome many limitations of traditional breeding, offering enormous potential for crop improvement and food production. Although the direct delivery of Cas9-single guide RNA (sgRNA) ribonucleoprotein (RNP) complexes to grapevine (Vitis vinifera) protoplasts has been shown before, the regeneration of edited protoplasts into whole plants has not been reported. Here, we describe an efficient approach to obtain transgene-free edited grapevine plants by the transfection and subsequent regeneration of protoplasts isolated from embryogenic callus. As proof of concept, a single-copy green fluorescent protein reporter gene (GFP) in the grapevine cultivar Thompson Seedless was targeted and knocked out by the direct delivery of RNPs to protoplasts. CRISPR/Cas9 activity, guided by two independent sgRNAs, was confirmed by the loss of GFP fluorescence. The regeneration of GFP− protoplasts into whole plants was monitored throughout development, confirming that the edited grapevine plants were comparable in morphology and growth habit to wild-type controls. We report the first highly efficient protocol for DNA-free genome editing in grapevine by the direct delivery of preassembled Cas9-sgRNA RNP complexes into protoplasts, helping to address the regulatory concerns related to genetically modified plants. This technology could encourage the application of genome editing for the genetic improvement of grapevine and other woody crop plants.
Natural variation in SlSOS2 promoter hinders salt resistance during tomato domestication
Authors: Hong Yechun , Guan Xijin , Wang Xu , Kong Dali , Yu Shuojun , Wang Zhiqiang , Yu Yongdong , Chao Zhen-Fei , Liu Xue , Huang Sanwen , Zhu Jian-Kang , Zhu Guangtao , Wang Zhen 
Published: October 2022

Abstract
Increasing soil salinization seriously impairs plant growth and development, resulting in crop loss. The Salt-Overly-Sensitive (SOS) pathway is indispensable to the mitigation of Na + toxicity in plants under high salinity. However, whether natural variations of SOS2 contribute to salt tolerance has not been reported. Here a natural variation in the SlSOS2 promoter region was identified to be associated with root Na+/K+ ratio and the loss of salt resistance during tomato domestication. This natural variation contains an ABI4-binding cis-element and plays an important role in the repression of SlSOS2 expression. Genetic evidence revealed that SlSOS2 mutations increase root Na+/K+ ratio under salt stress conditions and thus attenuate salt resistance in tomato. Together, our findings uncovered a critical but previously unknown natural variation of SOS2 in salt resistance, which provides valuable natural resources for genetic breeding for salt resistance in cultivated tomatoes and other crops.
Hematology and Machine Learning
Authors: Obstfeld Amrom E 
Published: October 2022

Abstract

Background
Substantial improvements in computational power and machine learning (ML) algorithm development have vastly increased the limits of what autonomous machines are capable of. Since its beginnings in the 19th century, laboratory hematology has absorbed waves of progress yielding improvements in both of accuracy and efficiency. The next wave of change in laboratory hematology will be the result of the ML revolution that has already touched many corners of healthcare and society at large.

Content
This review will describe the manifestations of ML and artificial intelligence (AI) already utilized in the clinical hematology laboratory. This will be followed by a topical summary of the innovative and investigational applications of this technology in each of the major subdomains within laboratory hematology.

Summary
Application of this technology to laboratory hematology will increase standardization and efficiency by reducing laboratory staff involvement in automatable activities. This will unleash time and resources for focus on more meaningful activities such as the complexities of patient care, research and development, and process improvement.
A multiwavelength study of multiple spectral component jets in AGN: testing the IC/CMB model for the large-scale-jet X-ray emission
Authors: Breiding Peter , Meyer Eileen T , Georganopoulos Markos , Reddy Karthik , Kollmann Kassidy E , Roychowdhury Agniva 
Published: October 2022

ABSTRACT
Over ∼150 resolved, kpc-scale X-ray jets hosted by active galactic nuclei have been discovered with the Chandra X-ray Observatory. A significant fraction of these jets have an X-ray spectrum either too high in flux or too hard to be consistent with the high-energy extension of the radio-to-optical synchrotron spectrum, a subtype we identify as Multiple Spectral Component (MSC) X-ray jets. A leading hypothesis for the origin of the X-rays is the inverse-Compton scattering of the cosmic microwave background by the same electron population producing the radio-to-optical synchrotron spectrum (known as the IC/CMB model). In this work, we test the IC/CMB model in 45 extragalactic X-ray jets using observations from the Fermi Large Area Telescope to look for the expected high level of gamma-ray emission, utilizing observations from the Atacama Large Millimeter/submillimeter Array (ALMA) and the Hubble Space Telescope (HST) when possible to best constrain the predicted gamma-ray flux. Including this and previous works, we now find the IC/CMB model to be ruled out in a total of 24/45 MSC X-ray jets due to its over-prediction for the observed MeV-to-GeV gamma-ray flux. We present additional evidence against the IC/CMB model, including the relative X-ray-to-radio relativistic beaming in these sources, and the general mismatch between radio and X-ray spectral indexes. Finally, we present upper limits on the large-scale bulk-flow Lorentz factors for all jets based on the Fermi upper limits, which suggest that these jets are at most mildly relativistic.
End-of-Life Care and Advanced Directives in Hispanic/Latinx Patients: Challenges and Solutions for the Practicing Oncologist
Authors: Barragan-Carrillo Regina , Pabon Cindy M , Chavarri-Guerra Yanin , Soto-Perez-de-Celis Enrique , Duma Narjust 
Published: October 2022

Abstract
Advanced end-of-life care (EOL) comprises a group of strategies to provide comfort to patients at the end of life. These are associated with better quality of life, better satisfaction, and a lower rate of hospitalizations and aggressive medical treatment. Advanced EOL care, including advanced directives completion and hospice enrollment, is suboptimal among Hispanic/Latinx patients with cancer due to personal, socio-cultural, financial, and health system-related barriers, as well as due to a lack of studies specifically designed for this population. In addition, the extrapolation of programs that increase participation in EOL for non-white Hispanics may not work appropriately for Hispanic/Latinx patients and lead to overall lower satisfaction and enrollment in EOL care. This review will provide the practicing oncologist with the tools to address EOL in the Hispanic/Latinx population. Some promising strategies to address the EOL care disparities in Latinx/Hispanic patients have been culturally tailored patient navigation programs, geriatric assessment-guided multidisciplinary interventions, counseling sessions, and educational interventions. Through these strategies, we encourage oncologists to take advantage of every clinical setting to discuss EOL care. Treating physicians can engage family members in caring for their loved ones while practicing cultural humility and respecting cultural preferences, incorporating policies to foster treatment for the underserved migrant population, and providing patients with validated Spanish language tools.
Integrated printed BDNF-stimulated HUCMSCs-derived exosomes/collagen/chitosan biological scaffolds with 3D printing technology promoted the remodelling of neural networks after traumatic brain injury
Authors: Liu Xiaoyin , Zhang Jian , Cheng Xu , Liu Peng , Feng Qingbo , Wang Shan , Li Yuanyou , Gu Haoran , Zhong Lin , Chen Miao , Zhou Liangxue 
Published: October 2022

Abstract
The restoration of nerve dysfunction after traumatic brain injury (TBI) faces huge challenges due to the limited self-regenerative abilities of nerve tissues. In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomes (MExos). In this study, brain-derived neurotrophic factor-stimulated HUCMSCs-derived exosomes (BMExos) were composited with collagen/chitosan by 3D printing technology. 3D-printed collagen/chitosan/BMExos (3D-CC-BMExos) scaffolds have excellent mechanical properties and biocompatibility. Subsequently, in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats. Consistent with the behavioural recovery, the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks, such as improving the regeneration of nerve fibres, synaptic connections and myelin sheaths, in lesions after TBI.
The nuclear bodies conference: Hubs of genomic activity, June 24–28, Western Shore, Nova Scotia, Canada
Authors: Kaufman Paul D. , Huang Sui , Pederson Thoru 
Published: October 2022

AbstractThis conference brought together leaders in the investigation of various bodies that populate the nucleus, a field that complements research on chromosome biology. These nuclear bodies had been receiving increasing attention as hubs of genome activity and the new findings reported at the conference strongly confirmed and significantly expanded this principle.
Evidence-based updates to the 2021 Surviving Sepsis Campaign guidelines
Authors: Lehman Karen D. 
Published: October 2022

Abstract:
Sepsis identification and treatment has changed significantly over the last few decades. Despite this, sepsis is still associated with significant morbidity and mortality. This first of a two-part series reviews the history of modern sepsis and presents new research in pathophysiology, treatment, and postsepsis care.
Pneumococcal vaccination for adults
Authors: Esden Jana L. 
Published: October 2022

Abstract:
Although pneumococcal vaccination programs have significantly reduced the incidence of pneumococcal infections in the US, pneumococcal pneumonia continues to be a burdensome cause of morbidity and mortality. Pneumococcal vaccination recommendation updates were recently published and introduce two new pneumococcal conjugate vaccines for use in adults ages 19 and older.
Current views on lupus in children
Authors: Smith Eve M.D. , Lythgoe Hanna , Hedrich Christian M. 
Published: October 2022

Purpose of review
This manuscript provides an update on clinical and pathophysiological features of juvenile-onset systemic lupus erythematosis (jSLE), challenges applying adult-derived classification criteria, and recent advances in treatment and care.

Recent findings
Significant scientific advances have improved the understanding of genetic factors (both genetic causes and risk alleles) and associated phenotypic features. Panels of urine/blood biomarker candidates aid in diagnosing jSLE, monitoring disease activity and predicting treatment response. Available classification criteria have been extensively assessed, with differences in clinical and immunological phenotypes of patients across age groups and ethnicities affecting their performance in jSLE. Therapeutic options remain limited and are based on protocols for adult-onset SLE patients. International efforts to inform development of a treat-to-target (T2T) approach for jSLE have yielded cohort-level evidence that target attainment reduces the risk of severe flare and new damage, and treatment compliance.

Summary
Recent studies have significantly improved our understanding of jSLE pathogenesis, highlighting important differences between jSLE and adult SLE, and providing the basis of biomarker development and target-directed individualized treatment and care. Future work focused on development of a T2T approach in jSLE is eagerly awaited.
Psychometric Testing of the Self-care of Coronary Heart Disease Inventory Version 3.0
Authors: Dickson Victoria Vaughan , Iovino Paolo , De Maria Maddalena , Vellone Ercole , Alvaro Rosaria , Di Matteo Roberta , Molin Alberto Dal , Lusignani Maura , Bassola Barbara , Maconi Antonio , Bolgeo Tatiana , Riegel Barbara 
Published: October 2022

Background
In this updated Self-Care of Coronary Heart Disease Inventory (SC-CHDI) v3.0, items were added to better reflect the theory of self-care of chronic illness and revised based on recent research. The expanded SC-CHDI now reflects the theoretical concepts of self-care maintenance, monitoring, and management.

Objective
The aim of this study was to evaluate the psychometric properties of the SC-CHDI v3.0.

Methods
In a sample of adults with coronary heart disease, we tested the SC-CHDI v3.0 validity with confirmatory factor analysis. Reliability was calculated using Cronbach α, factor score determinacy coefficient, and global reliability index for multidimensional scales, with values > 0.70 considered adequate.

Results
The sample (n = 205) was predominantly male (79%) with a mean age of 65.3 ± 11.1 years. The self-care maintenance scale encompassed 2 distinct behaviors, namely, “illness related behaviors” and “health promoting behaviors,” which reflect consulting and autonomous dimensions, respectively. The goodness-of-fit indices were adequate: χ2(25, N = 205) =31.86, P = .16, comparative fit index = 0.97, Tucker-Lewis Index = 0.95, root mean square error of approximation = 0.04 (90% confidence interval, 0.00–0.07), P = .705, and standardized root mean square residual = 0.045. Analysis of the new self-care monitoring scale yielded a single factor; goodness-of-fit indices were excellent: χ2(12, N = 205) =11.56, P = .48, comparative fit index = 1.00, Tucker-Lewis Index = 1.00, root mean square error of approximation < 0.001 (90% confidence interval, 0.000–0.07), P = .86, and standardized root mean square residual = 0.02. The self-care management scale had 2 dimensions of autonomous and consulting behavior with strong goodness-of-fit indices: χ2(7, N = 205) =6.57, P = .47, comparative fit index = 1.00, Tucker-Lewis Index = 1.00, root mean square error of approximation ≤ 0.001 (90% confidence interval, 0.00–0.08), P = .76, and standardized root mean square residual = 0.02. Reliability estimates were ≥0.80 for all scales.

Conclusions
Our testing suggests that the SC-CHDI v3.0 is a sound measure of the essential elements of self-care for adults with coronary heart disease.
Ventilation Scintigraphy With Radiolabeled Carbon Nanoparticulate Aerosol (Technegas)
Authors: Le Roux Pierre-Yves , Schafer Wolfgang M. , Blanc-Beguin Frédérique , Tulchinsky Mark 
Published: October 2022

Abstract
Invented and first approved for clinical use in Australia 36 years ago, Technegas is the technology that enabled ventilation scintigraphy with 99mTc-labeled carbon nanoparticles (99mTc-CNP). The US Food and Drug Administration (FDA) has considered this technology for more than 30 years but only now is getting close to approving it. Meanwhile, more than 4.4 million patients benefited from this technology in 64 countries worldwide. The primary application of 99mTc-CNP ventilation imaging is the diagnostic evaluation for suspicion of pulmonary embolism using ventilation-perfusion quotient (V/Q) imaging. Because of 99mTc-CNP's long pulmonary residence, tomographic imaging emerged as the preferred V/Q methodology. The FDA-approved ventilation imaging agents are primarily suitable for planar imaging, which is less sensitive. After the FDA approval of Technegas, the US practice will likely shift to tomographic V/Q. The 99mTc-CNP use is of particular interest in the COVID-19 pandemic because it offers an option of a dry radioaerosol that takes approximately only 3 to 5 tidal breaths, allowing the shortest exposure to and contact with possibly infected patients. Indeed, countries where 99mTc-CNP was approved for clinical use continued using it throughout the COVID-19 pandemic without known negative viral transmission consequences. Conversely, the ventilation imaging was halted in most US facilities from the beginning of the pandemic. This review is intended to familiarize the US clinical nuclear medicine community with the basic science of 99mTc-CNP ventilation imaging and its clinical applications, including common artifacts and interpretation criteria for tomographic V/Q imaging for pulmonary embolism.
Hyoepiglottic Rheumatoid Nodule Mimicking Head and Neck Malignancy on 18F-FDG PET/CT
Authors: Opalinski Ludwig , Schmitz Sandra , Van Eeckhout Pascal , d’Abadie Philippe , Gheysens Olivier 
Published: October 2022

Abstract
A 54-year-old man with a history of tonsillar squamous cell carcinoma treated with chemoradiotherapy and an 18-year history of seropositive rheumatoid arthritis in remission without maintenance therapy presented with right cervical pain and dysphagia for several months. Flexible laryngoscopy did not show any lesion, and MRI revealed a necrotic lesion inside the thyro-hyo-epiglottic space attached to the hyoid bone. 18F-FDG PET/CT demonstrated a moderately increased metabolic activity of the lesion without any other suspected lesions. Surgical resection was performed, and pathology revealed a necrotizing granuloma compatible with a rheumatoid nodule.
Fabrication of Molecular Blocks with High Responsiveness to the Cancer Microenvironment by Ursodeoxycholic Acid
Authors: Moroishi Kazuki , Nakamoto Masahiko , Matsusaki Michiya 
Published: October 2022

ABSTRACTIn cancer therapy, drug delivery system (DDS) has been widely studied to achieve selective drug accumulation at the tumor site. However, DDS still has a major drawback in that it requires multi-step processes for intracellular delivery, resulting in low efficiency of drug delivery. To overcome this problem, we recently reported a molecular block (MB) that disrupts cancer cell membranes in the cancer microenvironment using deoxycholic acid (DCA). However, the MB showed considerable cytotoxicity even at neutral pH possibly due to the structural hydrophobic property of DCA. Herein, we focused on selecting the most suitable bile acid for an MB that possessed high responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Cell viabilities of the free bile acids such as DCA, chenodeoxycholic acid (CDCA), cholic acid (CA) and ursodeoxycholic acid (UDCA) were evaluated at neutral pH (pH = 7.4) and a cancer acidic environment (pH = 6.3 ∼ 6.5). The half-maximal inhibition concentration (IC50) value of UDCA at pH = 7.4 showed an approximately 7.5-fold higher IC50value than that at pH = 6.3, whereas the other bile acids yielded less than a 4-fold IC50value difference between the same pHs. Biocompatible poly(vinyl alcohol) (PVA) was functionalized with UDCA (PVA-UDCA) for synthesis of higher responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Importantly, 56% pancreatic cancer cell death was observed at pH = 6.5, whereas only 10% was detected at neutral pH by the PVA-UDCA treatment. However, PVA-DCA indicated almost the same cancer cell death property independent of pH condition. These results suggest PVA-UDCA shows great potential for a new class of MB.
Fabrication of a Polymeric Inhibitor of Proximal Metabolic Enzymes in Hypoxia for Synergistic Inhibition of Cancer Cell Proliferation, Survival and Migration
Authors: Koba Yuki , Nakamoto Masahiko , Matsusaki Michiya 
Published: October 2022

ABSTRACTSince conventional molecular targeted drugs often result in side effect, the development of novel molecular targeted drugs with both high efficacy and selectivity are desired. Simultaneous inhibition of metabolically and spatiotemporally related proteins/enzymes is a promising strategy for improving therapeutic interventions in cancer treatment. Herein, we report a poly-α-L-glutamate-based polymer inhibitor that simultaneously targets proximal transmembrane enzymes under hypoxia, namely carbonic anhydrase IX (CAIX) and zinc-dependent metalloproteinases. A polymer incorporating two types of inhibitors more effectively inhibited the proliferation and migration of human breast cancer cells than a combination of two polymers functionalized exclusively with either inhibitor. Synergistic inhibition of cancer cells would occur owing to the hetero-multivalent interactions of the polymer with proximate enzymes on the cancer cell membrane. Our results highlight the potential of polymer-based cancer therapeutics.Abstract FigureFor Table of Contents only