bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oblique Alfvén waves in a stellar wind environment with dust particles charged by inelastic collisions and by photoionization
Authors: De Toni L B , Gaelzer R , Ziebell L F 
Published: February 2022

ABSTRACT
The characteristics of Alfvén waves propagating in a direction oblique to the ambient magnetic field in a stellar wind environment are discussed. A kinetic formulation for a magnetized dusty plasma is adopted considering Maxwellian distributions of electrons and ions, and immobile dust particles electrically charged by absorption of plasma particles and by photoionization. The dispersion relation is numerically solved and the results are compared with situations previously studied where dust particles were not charged by photoionization, which is an important process in a stellar wind of a relatively hot star. We show that the presence of dust causes the shear Alfvén waves to present a region of wavenumber values with zero frequency and that the minimum wavelength for which the mode becomes dispersive again is roughly proportional to the radiation intensity to which the dust grains are exposed. The damping rates of both shear and compressional Alfvén waves are observed to decrease with increasing radiation flux, for the parameters considered. For the particular case where both modes present a region with null real frequency when the radiation flux is absent or weak, it is shown that when the radiation flux is sufficiently strong, the photoionization mechanism may cause this region to get smaller or even to vanish, for compressional Alfvén waves. In that case, the compressional Alfvén waves present non-zero frequency for all wavenumber values, while the shear Alfvén waves still present null frequency in a certain interval of wavenumber values, which gets smaller with the presence of radiation.
A simple preparation protocol for shipping and storage of tissue sections for laser ablation-inductively coupled plasma-mass spectrometry imaging
Authors: Buchholz Rebecca , Krossa Sebastian , Andersen Maria K , Holtkamp Michael , Sperling Michael , Karst Uwe , Tessem May-Britt 
Published: February 2022

Abstract
A rapid and cost-efficient tissue preparation protocol for laser ablation-inductively coupled plasma-mass spectrometry imaging (LA–ICP–MSI) has been developed within this study as an alternative to the current gold standard using fresh-frozen samples or other preparation techniques such as formalin fixation (FFix) and formalin-fixed paraffin-embedding (FFPE). Samples were vacuum dried at room temperature (RT) and stored in sealed vacuum containers for storage and shipping between collaborating parties. We compared our new protocol to established methods using prostate tissue sections investigating typical endogenous elements such as zinc, iron, and phosphorous with LA–ICP–MSI. The new protocol yielded comparable imaging results as fresh-frozen sections. FFPE sections were also tested due to the wide use and availability of FFPE tissue. However, the FFPE protocol and the FFix alone led to massive washout of the target elements on the sections tested in this work. Therefore, our new protocol presents an easy and rapid alternative for tissue preservation with comparable results to fresh-frozen sections for LA–ICP–MSI. It overcomes washout risks of commonly used tissue fixation techniques and does not require expensive and potentially unstable and time-critical shipping of frozen material on dry ice. Additionally, this protocol is likely applicable for several bioimaging approaches, as the dry condition may act comparable to other dehydrating fixatives, such as acetone or methanol, preventing degradation while avoiding washout effects.
Characterization of the nickel-inserting cyclometallase LarC from Moorella thermoacetica and identification of a cytidinylylated reaction intermediate
Authors: Turmo Aiko , Hu Jian , Hausinger Robert P 
Published: February 2022

Abstract
LarC catalyzes the CTP-dependent insertion of nickel ion into pyridinium-3,5-bisthiocarboxylic acid mononucleotide (P2TMN), the final biosynthetic step for generating the nickel-pincer nucleotide (NPN) enzyme cofactor. In this study, we characterized a LarC homolog from Moorella thermoacetica (LarCMt) and characterized selected properties of the protein. We ruled out the hypothesis that enzyme inhibition by its product pyrophosphate accounts for its apparent single-turnover activity. Most notably, we identified a cytidinylylated-substrate intermediate that is formed during the reaction of LarCMt. Selected LarCMt variants with substitutions at the predicted CTP-binding site retained substantial amounts of activity, but exhibited greatly reduced levels of the CMP-P2TMN intermediate. In contrast, enhanced amounts of the CMP-P2TMN intermediate were generated when using LarCMt from cells grown on medium without supplemental nickel. On the basis of these results, we propose a functional role for CTP in the unprecedented nickel-insertase reaction during NPN biosynthesis.
Injectable hybrid inorganic nanoscaffold as rapid stem cell assembly template for cartilage repair
Authors: Wang Shenqiang , Yang Letao , Cai Bolei , Liu Fuwei , Hou Yannan , Zheng Hua , Cheng Fang , Zhang Hepeng , Wang Le , Wang Xiaoyi , Lv Qianxin , Kong Liang , Lee Ki-Bum , Zhang Qiuyu 
Published: February 2022

Abstract
Cartilage injuries are often devastating and most cannot be cured because of the intrinsically low regenerative capacity of cartilage tissues. Although stem-cell therapy has shown enormous potential for cartilage repair, the therapeutic outcome has been restricted by low survival rates and poor chondrocyte differentiation in vivo. Here, we report an injectable hybrid inorganic (IHI) nanoscaffold that facilitates fast assembly, enhances survival and regulates chondrogenic differentiation of stem cells. IHI nanoscaffolds that strongly bind to extracellular matrix (ECM) proteins assemble stem cells through synergistic 3D cell–cell and cell–matrix interactions, creating a favorable physical microenvironment for stem-cell survival and differentiation in vitro and in vivo. Additionally, chondrogenic factors can be loaded into nanoscaffolds with a high capacity, which allows deep, homogenous drug delivery into assembled 3D stem-cell-derived tissues for effective control over the soluble microenvironment of stem cells. The developed IHI nanoscaffolds that assemble with stem cells are injectable. They also scavenge reactive oxygen species and timely biodegrade for proper integration into injured cartilage tissues. Implantation of stem-cell-assembled IHI nanoscaffolds into injured cartilage results in accelerated tissue regeneration and functional recovery. By establishing our IHI nanoscaffold-templated 3D stem-cell assembly method, we provide a promising approach to better overcoming the inhibitory microenvironment associated with cartilage injuries and to advance current stem-cell-based tissue engineering.
Long-term Outcomes and Recovery of Patients who Survived COVID-19: LUNG INJURY COVID-19 Study
Authors: Vargas Centanaro Gianna , Calle Rubio Myriam , Álvarez-Sala Walther José Luis , Martinez-Sagasti Fernando , Albuja Hidalgo Andrea , Herranz Hernández Rafael , Rodríguez Hermosa Juan Luis 
Published: February 2022

Abstract

Background
LUNG INJURY COVID-19 (clinicaltrials.gov NCT 21/399-E) is a registry-based prospective observational cohort study to evaluate long-term outcomes and recovery 12 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection according to severity.

Methods
Three hundred five coronavirus disease 2019 (COVID-19) survivors were included (moderate, 162; severe, 143). Twelve months after SARS-CoV-2 infection, there was resolution of respiratory symptoms (37.9% in severe vs 27.3% in moderate pneumonia; P = .089).

Results
Exertional dyspnea was present (20% in severe vs 18.4% in moderate; P = .810). Abnormalities on chest radiology imaging were detected more often in severe COVID-19 infection vs moderate infection (29% vs 8.8%; P &lt; .001). Pulmonary function testing (forced spirometry or diffusion) performed at 12 months of mean follow-up according to protocol detected anomalies in 31.4% of patients with severe COVID-19 courses and in 27.7% of moderate patients. Risk factors associated with diffusion impairment at 12 months were age (odds ratio [OR], 1.05; 95% CI, 1.01–1.10; P = .008), forced expiratory volume in 1 second predicted at follow-up (OR, 0.96; 95% CI, 0.93–0.99; P = .017), and dyspnea score at follow-up (OR, 3.16; 95% CI, 1.43–6.97; P = .004). Computed tomography (CT) scans performed at 12 months of mean follow-up showed evidence of fibrosis in almost half of patients with severe COVID-19 courses, who underwent CT according to protocol.

Conclusions
At 12 months from infection onset, most patients refer to symptoms, particularly muscle weakness and dyspnea, and almost one-third of patients with severe COVID-19 pneumonia had impaired pulmonary diffusion and abnormalities on chest radiology imaging. These results emphasize the importance of systematic follow-up after severe COVID-19, with appropriate management of pulmonary sequelae.
Pentatricopeptide repeat protein CNS1 regulates maize mitochondrial complex III assembly and seed development
Authors: Ma Shuai , Yang Wenzhu , Liu Xiaoqing , Li Suzhen , Li Ye , Zhu Jiameng , Zhang Chunyi , Lu Xiaoduo , Zhou Xiaojin , Chen Rumei 
Published: February 2022

Abstract
Mitochondrial function relies on the assembly of electron transport chain complexes, which requires coordination between proteins encoded by the mitochondrion and those of the nucleus. Here, we cloned a maize (Zea mays) cytochrome c maturation FN stabilizer1 (CNS1) and found it encodes a pentatricopeptide repeat (PPR) protein. Members of the PPR family are widely distributed in plants and are associated with RNA metabolism in organelles. P-type PPR proteins play essential roles in stabilizing the 3′-end of RNA in mitochondria; whether a similar process exists for stabilizing the 5′-terminus of mitochondrial RNA remains unclear. The kernels of cns1 exhibited arrested embryo and endosperm development, whereas neither conventional splicing deficiency nor RNA editing difference in mitochondrial genes was observed. Instead, most of the ccmFN transcripts isolated from cns1 mutant plants were 5′-truncated and therefore lacked the start codon. Biochemical and molecular data demonstrated that CNS1 is a P-type PPR protein encoded by nuclear DNA and that it localizes to the mitochondrion. Also, one binding site of CNS1 located upstream of the start codon in the ccmFN transcript. Moreover, abnormal mitochondrial morphology and dramatic upregulation of alternative oxidase genes were observed in the mutant. Together, these results indicate that CNS1 is essential for reaching a suitable level of intact ccmFN transcripts through binding to the 5′-UTR of the RNAs and maintaining 5′-integrity, which is crucial for sustaining mitochondrial complex III function to ensure mitochondrial biogenesis and seed development in maize.
Ruxolitinib inhibits IFNγ-stimulated Sjögren’s salivary gland MSC HLA-DR expression and chemokine-dependent T cell migration
Authors: McCoy Sara S , Parker Maxwell , Gurevic Ilya , Das Rahul , Pennati Andrea , Galipeau Jacques 
Published: February 2022

AbstractObjectivesSjögren’s disease (SjD) is a systemic autoimmune disease characterized by focal lymphocytic infiltrate of salivary glands (SGs) and high SG IFNγ, both of which are associated with elevated lymphoma risk. IFNγ is also biologically relevant to mesenchymal stromal cells (MSCs), a SG resident cell with unique niche regenerative and immunoregulatory capacities. In contrast to the role of IFNγ in SjD, IFNγ promotes an anti-inflammatory MSC phenotype in other diseases. The objective of this study was to define the immunobiology of IFNγ-exposed SG-MSCs with and without the JAK1 & 2 inhibitor, ruxolitinib.MethodsSG-MSCs were isolated from SjD and controls human subjects. SG-MSCs were treated with 10 ng/ml IFNγ +/– 1000 nM ruxolitinib. Experimental methods included flow cytometry, RNA-sequencing, chemokine array, ELISA and transwell chemotaxis experiments.ResultsWe found that IFNγ promoted expression of SG-MSC immunomodulatory markers, including HLA-DR, and this expression was inhibited by ruxolitinib. We confirmed the differential expression of CXCL9, CXCL10, CXCL11, CCL2 and CCL7, initially identified with RNA sequencing. SG-MSCs promoted CD4+ T cell chemotaxis when pre-stimulated with IFNγ. Ruxolitinib blocks chemotaxis through inhibition of SG-MSC production of CXCL9, CXCL10 and CXCL11.ConclusionsThese findings establish that ruxolitinib inhibits IFNγ-induced expression of SG-MSC immunomodulatory markers and chemokines. Ruxolitinib also reverses IFNγ-induced CD4+ T cell chemotaxis, through inhibition of CXCL9, -10 and -11. Because IFNγ is higher in SjD than control SGs, we have identified SG-MSCs as a plausible pathogenic cell type in SjD. We provide proof of concept supporting further study of ruxolitinib to treat SjD.
Use of Physiologically Based Kinetic Modeling-Facilitated Reverse Dosimetry to PredictIn VivoAcute Toxicity of Tetrodotoxin in Rodents
Authors: Noorlander Annelies , Zhang Mengying , van Ravenzwaay Bennard , Rietjens Ivonne M C M 
Published: February 2022

AbstractIn this study, the ability of a new in vitro/in silico quantitative in vitro–in vivo extrapolation (QIVIVE) methodology was assessed to predict the in vivo neurotoxicity of tetrodotoxin (TTX) in rodents. In vitro concentration–response data of TTX obtained in a multielectrode array assay with primary rat neonatal cortical cells and in an effect study with mouse neuro-2a cells were quantitatively extrapolated into in vivo dose–response data, using newly developed physiologically based kinetic (PBK) models for TTX in rats and mice. Incorporating a kidney compartment accounting for active renal excretion in the PBK models proved to be essential for its performance. To evaluate the predictions, QIVIVE-derived dose–response data were compared with in vivo data on neurotoxicity in rats and mice upon oral and parenteral dosing. The results revealed that for both rats and mice the predicted dose–response data matched the data from available in vivo studies well. It is concluded that PBK modeling-based reserve dosimetry of in vitro TTX effect data can adequately predict the in vivo neurotoxicity of TTX in rodents, providing a novel proof-of-principle for this methodology.
PtaERF194 inhibits plant growth and enhances drought tolerance in poplar
Authors: Wang Shengji , Fan Yan , Du Shuhui , Zhao Kai , Liu Qiang , Yao Wenjing , Zheng Tangchun , Han Youzhi 
Published: February 2022

Abstract
The water deficits limit the growth and development of agricultural and forest organisms. The AP2/ethylene response factor (ERF) family has been identified as one of the largest plant-specific transcription factors (TFs) essential for plant development and stress response. The function of PtaERF194 in growth and drought tolerance was detected in the overexpression (OX) and RNA interference (RNAi) transgenic poplar 717 hybrids (Populus tremula × Populus alba). Plant growth, stem vessels, water-use efficiency (WUE), chlorophyll content and PtaERF194 co-expressed genes were analyzed using morphological, physiological and molecular methods. Overexpression seedlings showed a shorter and smaller phenotype along with smaller and more vessels compared with the wild-type (WT). Physiological indices indicated that OX with low transpiration and stomatal conductance improved the tolerance to drought by enhancing WUE, limiting water loss and maintaining high water potential. A total of 12 differentially expressed genes co-expressed with PtaERF194 were identified, and they worked together to regulate drought tolerance through the abscisic acid signaling and reactive oxygen species scavenging processes. However, RNAi plants showed similar morphology and physiology to WT, suggesting that the function of PtaERF194 was redundant with other ERF TFs. The findings of the current study may shed new light on the positive function of ERF TFs in plant drought stress tolerance.
The Stanford Global Health Media Fellowship: Training the Next Generation of Physician Communicators to Fight Health Misinformation
Authors: Krohn Kristina M. , Yu Gina , Lieber Mark , Barry Michele 
Published: February 2022

Problem
The COVID-19 pandemic and the spread of related health misinformation, especially on social media, have highlighted the need for more health care professionals to produce and share accurate health information to improve health and health literacy. Yet, few programs address this problem by training health care professionals in the art of science writing and medical journalism.

Approach
Created in 2011, the Stanford Global Health Media Fellowship aims to train medical students and residents in public communication strategies. Each year, 1 physician-in-training is selected to complete the fellowship, which includes 3 rotations: (1) 1 academic quarter at Stanford’s Graduate Program in Journalism, (2) 3 to 5 months with a national news network (previously NBC and ABC, now CNN), and (3) a placement at an international site. During the year-long program, fellows also complete a capstone project tackling a global health equity issue.

Outcomes
Since 2011, 10 fellows have completed the program, and they have acquired skills in reporting, writing, multimedia, social media, and medical communications. During the news network rotation, they have completed more than 200 medical news pieces and improved the quality of the health information in a myriad of other pieces. Alumni have continued to write and report on medical stories throughout residency, other fellowships, and as practicing physicians. One alumnus is now a medical news producer at CNN.

Next Steps
Expanding high-quality training in medical journalism for physicians through partnerships with journalism schools; communications departments; and local, national, and international journalists can greatly improve physicians’ ability to communicate with the public. It also has the potential to greatly improve the health information the public receives. Educators should consider embedding mass health communications training in medical education curricula and increasing opportunities for physicians to engage with diverse public audiences.
Smoking During Pregnancy and Risk of Attention-deficit/Hyperactivity Disorder in the Third Generation
Authors: Yim Gyeyoon , Roberts Andrea , Ascherio Alberto , Wypij David , Kioumourtzoglou Marianthi-Anna , Weisskopf and Marc G. 
Published: February 2022

Background:
Animal experiments indicate that environmental factors, such as cigarette smoke, can have multigenerational effects through the germline. However, there are little data on multigenerational effects of smoking in humans. We examined the associations between grandmothers’ smoking while pregnant and risk of attention-deficit/hyperactivity disorder (ADHD) in her grandchildren.

Methods:
Our study population included 53,653 Nurses’ Health Study II (NHS-II) participants (generation 1 [G1]), their mothers (generation 0 [G0]), and their 120,467 live-born children (generation 2 [G2]). In secondary analyses, we used data from 23,844 mothers of the nurses who were participants in the Nurses’ Mothers’ Cohort Study (NMCS), a substudy of NHS-II.

Results:
The prevalence of G0 smoking during the pregnancy with the G1 nurse was 25%. ADHD was diagnosed in 9,049 (7.5%) of the grandchildren (G2). Grand-maternal smoking during pregnancy was associated with increased odds of ADHD among the grandchildren (adjusted odds ratio [aOR] = 1.2; 95% confidence interval [CI] = 1.1, 1.2), independent of G1 smoking during pregnancy. In the Nurses’ Mothers’ Cohort Study, odds of ADHD increased with increasing cigarettes smoked per day by the grandmother (1–14 cigarettes: aOR = 1.1; 95% CI = 1.0, 1.2; 15+: aOR = 1.2; 95% CI = 1.0, 1.3), compared with nonsmoking grandmothers.

Conclusions:
Grandmother smoking during pregnancy is associated with an increased risk of ADHD among the grandchildren.
Estimation of Relative Vaccine Effectiveness in Influenza: A Systematic Review of Methodology
Authors: McMenamin Martina E. , Bond Helen S. , Sullivan Sheena G. , Cowling Benjamin J. 
Published: February 2022

Background:
When new vaccine components or platforms are developed, they will typically need to demonstrate noninferiority or superiority over existing products, resulting in the assessment of relative vaccine effectiveness (rVE). This review aims to identify how rVE evaluation is being performed in studies of influenza to inform a more standardized approach.

Methods:
We conducted a systematic search on PubMed, Google Scholar, and Web of Science for studies reporting rVE comparing vaccine components, dose, or vaccination schedules. We screened titles, abstracts, full texts, and references to identify relevant articles. We extracted information on the study design, relative comparison made, and the definition and statistical approach used to estimate rVE in each study.

Results:
We identified 63 articles assessing rVE in influenza virus. Studies compared multiple vaccine components (n = 38), two or more doses of the same vaccine (n = 17), or vaccination timing or history (n = 9). One study compared a range of vaccine components and doses. Nearly two-thirds of all studies controlled for age, and nearly half for comorbidities, region, and sex. Assessment of 12 studies presenting both absolute and relative effect estimates suggested proportionality in the effects, resulting in implications for the interpretation of rVE effects.

Conclusions:
Approaches to rVE evaluation in practice is highly varied, with improvements in reporting required in many cases. Extensive consideration of methodologic issues relating to rVE is needed, including the stability of estimates and the impact of confounding structure on the validity of rVE estimates.
POLYPOIDAL CHOROIDAL NEOVASCULARIZATION VERSUS TYPE 1 CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION
Authors: Serra Rita , Coscas Florence , Cabral Diogo , Pinna Antonio , Coscas Gabriel 
Published: February 2022

Purpose:
To compare quantitative optical coherence tomography angiography parameters between polypoidal choroidal neovascularizations (PCNVs) and Type 1 choroidal neovascularizations (CNVs) in patients with age-related macular degeneration.

Methods:
PCNV and Type 1 CNV lesions were retrospectively recruited in a cohort of patients with age-related macular degeneration. All the patients underwent a comprehensive ophthalmic evaluation, including best-corrected visual acuity, fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT), and optical coherence tomography angiography.
Vascular perfusion density, fractal dimension, and lacunarity were computed by means of fractal analysis of neovascular en face optical coherence tomography angiography slabs.

Results:
Sixty-eight eyes were included in the analysis. Of them, 35 of 68 eyes (51.5%) had PCNV and 33 of 68 (48.5%) had Type 1 CNV. Patients with PCNV were significantly younger (P = 0.0003) and had a higher best-corrected visual acuity (P < 0.0001). The mean vascular perfusion density was 0.83 ± 0.11% in PCNVs and 0.46 ± 0.10% in Type 1 CNVs (P < 0.0001). The mean fractal dimension was 1.44 ± 0.1 in PCNVs and 1.45 ± 0.09 in Type 1 CNVs (P = 0.86) while the mean lacunarity was 2.46 ± 1.03 in PCNVs and 1.86 ± 0.52 in Type 1 CNVs (P = 0.006).

Conclusion:
PCNVs resulted to be more heterogeneous and characterized by higher vascular perfusion density and lacunarity values than Type 1 CNVs. These interesting findings seem to support the idea that PCNVs and Type 1 CNVs are two separate clinical entities. However, future studies based on optical coherence tomography angiography fractal analysis, but also involving other relevant parameters such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions on whether PCNV is a specific clinical entity or a neovascular age-related macular degeneration variant.