bluuebunny/crossref_metadata_2025 huggingface dataset:
Widespread RNA hypoediting in schizophrenia and its relevance to mitochondrial function
Authors: Choudhury Mudra , Fu Ting , Amoah Kofi , Jun Hyun-Ik , Chan Tracey W. , Park Sungwoo , Walker David W. , Bahn Jae Hoon , Xiao Xinshu
Published: April 2023

RNA editing, the endogenous modification of nucleic acids, is known to be altered in genes with important neurological function in schizophrenia (SCZ). However, the global profile and molecular functions of disease-associated RNA editing remain unclear. Here, we analyzed RNA editing in postmortem brains of four SCZ cohorts and uncovered a significant and reproducible trend of hypoediting in patients of European descent. We report a set of SCZ-associated editing sites via WGCNA analysis, shared across cohorts. Using massively parallel reporter assays and bioinformatic analyses, we observed that differential 3′ untranslated region (3′UTR) editing sites affecting host gene expression were enriched for mitochondrial processes. Furthermore, we characterized the impact of two recoding sites in the mitofusin 1 (MFN1) gene and showed their functional relevance to mitochondrial fusion and cellular apoptosis. Our study reveals a global reduction of editing in SCZ and a compelling link between editing and mitochondrial function in the disease.
Increased U.S. coastal hurricane risk under climate change
Authors: Balaguru Karthik , Xu Wenwei , Chang Chuan-Chieh , Leung L. Ruby , Judi David R. , Hagos Samson M. , Wehner Michael F. , Kossin James P. , Ting Mingfang
Published: April 2023

Several pathways for how climate change may influence the U.S. coastal hurricane risk have been proposed, but the physical mechanisms and possible connections between various pathways remain unclear. Here, future projections of hurricane activity (1980–2100), downscaled from multiple climate models using a synthetic hurricane model, show an enhanced hurricane frequency for the Gulf and lower East coast regions. The increase in coastal hurricane frequency is driven primarily by changes in steering flow, which can be attributed to the development of an upper-level cyclonic circulation over the western Atlantic. The latter is part of the baroclinic stationary Rossby waves forced mainly by increased diabatic heating in the eastern tropical Pacific, a robust signal across the multimodel ensemble. Last, these heating changes also play a key role in decreasing wind shear near the U.S. coast, further aggravating coastal hurricane risk enhanced by the physically connected steering flow changes.
Mechanically reconfigurable van der Waals devices via low-friction gold sliding
Authors: Barabas Andrew Z. , Sequeira Ian , Yang Yuhui , Barajas-Aguilar Aaron H. , Taniguchi Takashi , Watanabe Kenji , Sanchez-Yamagishi Javier D.
Published: April 2023

Interfaces of van der Waals (vdW) materials, such as graphite and hexagonal boron nitride (hBN), exhibit low-friction sliding due to their atomically flat surfaces and weak vdW bonding. We demonstrate that microfabricated gold also slides with low friction on hBN. This enables the arbitrary post-fabrication repositioning of device features both at ambient conditions and in situ to a measurement cryostat. We demonstrate mechanically reconfigurable vdW devices where device geometry and position are continuously tunable parameters. By fabricating slidable top gates on a graphene-hBN device, we produce a mechanically tunable quantum point contact where electron confinement and edge-state coupling can be continuously modified. Moreover, we combine in situ sliding with simultaneous electronic measurements to create new types of scanning probe experiments, where gate electrodes and even entire vdW heterostructure devices can be spatially scanned by sliding across a target.
Ultrathin, soft, radiative cooling interfaces for advanced thermal management in skin electronics
Authors: Li Jiyu , Fu Yang , Zhou Jingkun , Yao Kuanming , Ma Xue , Gao Shouwei , Wang Zuankai , Dai Jian-Guo , Lei Dangyuan , Yu Xinge
Published: April 2023

Thermal management plays a notable role in electronics, especially for the emerging wearable and skin electronics, as the level of integration, multifunction, and miniaturization of such electronics is determined by thermal management. Here, we report a generic thermal management strategy by using an ultrathin, soft, radiative-cooling interface (USRI), which allows cooling down the temperature in skin electronics through both radiative and nonradiative heat transfer, achieving temperature reduction greater than 56°C. The light and intrinsically flexible nature of the USRI enables its use as a conformable sealing layer and hence can be readily integrated with skin electronics. Demonstrations include passive cooling down of Joule heat for flexible circuits, improving working efficiency for epidermal electronics, and stabling performance outputs for skin-interfaced wireless photoplethysmography sensors. These results offer an alternative pathway toward achieving effective thermal management in advanced skin-interfaced electronics for multifunctionally and wirelessly operated health care monitoring.
Computational prediction of MHC anchor locations guides neoantigen identification and prioritization
Authors: Xia Huiming , McMichael Joshua , Becker-Hapak Michelle , Onyeador Onyinyechi C. , Buchli Rico , McClain Ethan , Pence Patrick , Supabphol Suangson , Richters Megan M. , Basu Anamika , Ramirez Cody A. , Puig-Saus Cristina , Cotto Kelsy C. , Freshour Sharon L. , Hundal Jasreet , Kiwala Susanna , Goedegebuure S. Peter , Johanns Tanner M. , Dunn Gavin P. , Ribas Antoni , Miller Christopher A. , Gillanders William E. , Fehniger Todd A. , Griffith Obi L. , Griffith Malachi
Published: April 2023

Neoantigens are tumor-specific peptide sequences resulting from sources such as somatic DNA mutations. Upon loading onto major histocompatibility complex (MHC) molecules, they can trigger recognition by T cells. Accurate neoantigen identification is thus critical for both designing cancer vaccines and predicting response to immunotherapies. Neoantigen identification and prioritization relies on correctly predicting whether the presenting peptide sequence can successfully induce an immune response. Because most somatic mutations are single-nucleotide variants, changes between wild-type and mutated peptides are typically subtle and require cautious interpretation. A potentially underappreciated variable in neoantigen prediction pipelines is the mutation position within the peptide relative to its anchor positions for the patient’s specific MHC molecules. Whereas a subset of peptide positions are presented to the T cell receptor for recognition, others are responsible for anchoring to the MHC, making these positional considerations critical for predicting T cell responses. We computationally predicted anchor positions for different peptide lengths for 328 common HLA alleles and identified unique anchoring patterns among them. Analysis of 923 tumor samples shows that 6 to 38% of neoantigen candidates are potentially misclassified and can be rescued using allele-specific knowledge of anchor positions. A subset of anchor results were orthogonally validated using protein crystallography structures. Representative anchor trends were experimentally validated using peptide-MHC stability assays and competition binding assays. By incorporating our anchor prediction results into neoantigen prediction pipelines, we hope to formalize, streamline, and improve the identification process for relevant clinical studies.
Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation
Authors: Fabre Thomas , Barron Alexander M. S. , Christensen Stephen M. , Asano Shoh , Bound Kathryn , Lech Matthew P. , Wadsworth Marc H. , Chen Xiao , Wang Chang , Wang Ju , McMahon James , Schlerman Franklin , White Alexis , Kravarik Kellie M. , Fisher Andrew J. , Borthwick Lee A. , Hart Kevin M. , Henderson Neil C. , Wynn Thomas A. , Dower Ken
Published: April 2023

Macrophages are central orchestrators of the tissue response to injury, with distinct macrophage activation states playing key roles in fibrosis progression and resolution. Identifying key macrophage populations found in human fibrotic tissues could lead to new treatments for fibrosis. Here, we used human liver and lung single-cell RNA sequencing datasets to identify a subset of

CD9
+
TREM2
+

macrophages that express
SPP1
,
GPNMB
,
FABP5
, and
CD63
. In both human and murine hepatic and pulmonary fibrosis, these macrophages were enriched at the outside edges of scarring and adjacent to activated mesenchymal cells. Neutrophils expressing MMP9, which participates in the activation of TGF-β1, and the type 3 cytokines GM-CSF and IL-17A coclustered with these macrophages. In vitro, GM-CSF, IL-17A, and TGF-β1 drive the differentiation of human monocytes into macrophages expressing scar-associated markers. Such differentiated cells could degrade collagen IV but not collagen I and promote TGF-β1–induced collagen I deposition by activated mesenchymal cells. In murine models blocking GM-CSF, IL-17A or TGF-β1 reduced scar-associated macrophage expansion and hepatic or pulmonary fibrosis. Our work identifies a highly specific macrophage population to which we assign a profibrotic role across species and tissues. It further provides a strategy for unbiased discovery, triage, and preclinical validation of therapeutic targets based on this fibrogenic macrophage population.
Vulvar reconstruction in post-RT case using the versatile VRAM flap: reporting the rare extrapelvic approach
Authors: Baruah Upasana , Tak Apoorva , Barmon Debabrata , Begum Dimpy
Published: April 2023

Although primary vulvovaginal reconstruction following vulvectomy has a significant chance of improving patient outcomes, flap reconstruction is not a recognised component of the accepted standard of care for vulvar cancer. We provide a case of a patient who underwent successful vulvar reconstruction using the extrapelvic vertical rectus abdominis myocutaneous (VRAM) flap. This musculocutaneous flap offers adequate coverage and bulk to the perineal defect after excision in post-irradiated vulvar cancer.

To proceed with sphincter-saving surgery, she was scheduled for neoadjuvant chemoradiation, as the lesion involved the urethra and perineal body. However, she experienced severe grade IV dermatitis after receiving 37 Gy of radiation. Though the lesion had reduced in size, it was still large enough to cause significant perineal deformity.

We performed a vulvar reconstructive surgery using the uncommon but reliable extrapelvic VRAM flap. This well-vascularised VRAM flap is particularly useful in irradiated areas prone to poor healing. Postoperatively, the wound healed well and the patient underwent adjuvant therapy 6 weeks later. We emphasise the advantages of well-perfused muscle for the primary repair of prior irradiated perineal lesions.
Anal canal gastrointestinal stromal tumour (GIST)
Authors: Brucchi Francesco , Lauricella Sara , Bottero Luca , Faillace Giuseppe Giacomo
Published: April 2023

Gastrointestinal stromal tumours (GISTs) are malignant mesenchymal tumours that originate from the interstitial pacemaker cells of Cajal. They are particularly rare, comprising only 5% of all GISTs, and often present at an advanced stage. Treatment for these tumours is still a topic of debate due to their low incidence and insidious location. A woman in her mid-70s presented with rectal bleeding and anal discomfort. A 4.5×4 cm anal GIST was diagnosed. A local excision was performed and the patient was further treated with tyrosine kinase inhibitors. At a 6-month follow-up, the MRI showed that she was disease free. Anorectal GISTs are unusual and tend to be aggressive. Surgical resection is the first-line treatment for primary, localised GISTs. However, the appropriate surgical technique for these tumours is still a topic of debate. Further studies are needed to fully understand the oncologic behaviour of these rare neoplasms.
‘Just because something works doesn’t mean it can’t be improved’: an ethnographic analysis of the health system inBlack Panther’sWakanda
Authors: Jackson Jennifer , Ferreira Carla , Scott Melissa , Barah Elke Jaibeeh , Upal Zahra , Phelps Krista , Mei Carol , Woo Haneul , Tung Megan , Gadimova Farida , Ewanyshyn Alexandra , Perry Samantha , Ens Twyla , Ginn Carla
Published: April 2023

The emergence of COVID-19 (SARS-CoV-2) has introduced significant global challenges for healthcare systems, healthcare professionals and patients. This current climate creates an opportunity to learn from equitable health systems and move toward making fundamental changes to healthcare systems. Our ethnographic analysis of Wakanda’s healthcare system inBlack Panther, from theMarvel Cinematic Universe, offers opportunities for system-level transformation across healthcare settings. We propose four healthcare system themes within the context of Wakandan identity: (1) technology as an instrument (blending bodies and technology, blending technology with tradition); (2) reimagining medication; (3) warfare and rehabilitation; and (4) preventative approaches to health (prioritising collective health, deprofessionalisation of healthcare services). The preceding themes represent core elements of Wakandan health systems that allow the people of Wakanda to thrive. Wakandans retain a strong identity and cultural traditions while embracing modern technologies. We found that effective upstream approaches to health for all are embedded in anti-colonial philosophies. Wakandans embrace innovation, embedding biomedical engineering and continuous improvement into care settings. For global health systems under strain, Wakanda’s health system identifies equitable possibilities for system change, reminding us that culturally relevant prevention strategies can both decrease pressure on health services and allow all people to thrive.
Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety
Authors: Fernández Pérez Evans R , Crooks James L , Lynch David A , Humphries Stephen M , Koelsch Tilman L , Swigris Jeffrey J , Solomon Joshua J , Mohning Michael P , Groshong Steve D , Fier Kaitlin
Published: April 2023

Background

Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients.

Methods

We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety.

Results

After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference −0.76%, 95% CI −6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events.

Conclusions

The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP.

Trial registration mumber

NCT02958917.
Incorporating protected areas into global fish biomass projections under climate change
Authors: Palacios-Abrantes Juliano , Roberts Sarah M. , ten Brink Talya , Cashion Tim , Cheung William W.L. , Mook Anne , Nguyen Tu
Published: April 2023

The world has set ambitious goals to protect marine biodiversity and improve ocean health in the face of anthropogenic threats. Yet, the efficiency of spatial tools such as marine reserves to protect biodiversity is threatened as climate change shifts species distributions globally. Here, we investigate the ability of global marine reserves to protect fish biomass under future climate change scenarios. Moreover, we explore regional patterns and compare worlds with and without marine reserves. We rely on computer modeling to simulate an utopian world where all marine reserves thrive and ocean governance is effective. Results suggest that climate change will affect fish biomass in most marine reserves and their surrounding waters throughout the 21st century. The biomass change varies among regions, with tropical reserves losing biomass, temperate ones gaining, and polar reserves having mixed effects. Overall, a world with marine reserves will still be better off in terms of fish biomass than a world without marine reserves. Our study highlights the need to promote climate resilient conservation methods if we are to maintain and recover biodiversity in the ocean under a changing world.
Designing a Framework for Conversational Interfaces
Authors: Tellman Zachary
Published: April 2023

Wherever possible, business logic should be described by code rather than training data. This keeps our system's behavior principled, predictable, and easy to change. Our approach to conversational interfaces allows them to be built much like any other application, using familiar tools, conventions, and processes, while still taking advantage of cutting-edge machine-learning techniques.
Analytical and Approximate Solutions of the Nonlinear Gas Dynamic Equation Using a Hybrid Approach
Authors: Nadeem Muhammad , Ali Mouad M. H.
Published: April 2023

This paper presents the study of a numerical scheme for the analytical solution of nonlinear gas dynamic equation. We use the idea of Laplace–Carson transform and associate it with the homotopy perturbation method (HPM) for obtaining the series solution of the equation. We show that this hybrid approach is excellent in agreement and converges to the exact solution very smoothly. Further, HPM combined with He’s polynomial is utilized to minimize the numerical simulations in nonlinear conditions that make it easy for the implementation of Laplace–Carson transform. We also exhibit a few graphical solutions to indicate that this approach is extremely reliable and convenient for linear and nonlinear challenges.
Functional Evaluation of Percutaneous Coronary Intervention Based on CT Images of Three-Dimensional Reconstructed Coronary Artery Model
Authors: Fu Dongliang , Liu Mengru , Shao Mingjing , Mao Yijin , Li Chunyan , Jiang Hong , Li Xianlun
Published: April 2023

In order to explore the computerized tomography (CT) based on three-dimensional reconstruction of coronary artery model, the functional evaluation was made after percutaneous coronary intervention (PCI). In this study, 90 patients with coronary heart disease who received elective PCI were selected. The blood flow reserve fraction (FFR) and SYNTAX score were calculated by three-dimensional reconstruction of CT images, followed up for 2–4 years. According to the SYNTAX score, 0–22 points were defined as the low group (28 cases), 23–32 points as the medium group (33 cases), and 33 points as the high group (29 cases). In this paper, the accuracy, sensitivity, and specificity of CT images of three-dimensional reconstructed coronary artery model are 91%, 73%, and 62%, respectively. The follow-up results showed that the incidence of major adverse cerebrovascular events in the high group was significantly higher than that in the low group and the middle group, and the difference was statistically significant (

P
<
0.05

). Pearson correlation analysis showed that SYNTAX score was related to serum total cholesterol (r = 0.234,

P
=
0.003

), triglyceride (r = 0.237,

P
=
0.014

), low-density lipoprotein cholesterol (r = 0.285,

P
=
0.004

), and ApoB/ApoA1 (R = 0.004). In this study, FFR is calculated by CT images based on three-dimensional reconstruction of coronary artery model, which can provide support for the diagnosis and treatment of coronary heart disease. SYNTAX score can be used as a risk predictor for PCI patients with coronary heart disease.
Self-Expanding Versus Balloon Expanding Coronary Stents in Intervention of the Degenerated Saphenous Vein Graft: Memmingen Coronary Artery Bypass Stenosis Trial (MECAST)
Authors: Siry Marcus , Duymaz Burak , Biesenberger Simon , Siry Deborah , Kammerer Vanessa , May Andreas E.
Published: April 2023

Objectives. The aim of this retrospective analysis was to compare the patient outcome after interventional therapy of saphenous vein graft (SVG) stenoses in an all-comers population receiving either self-expanding drug-eluting stents (SExS) or balloon expanding drug-eluting stents (BExS). Background. The interventional therapy of degenerated SVGs remains challenging. Diameter variations of stenotic segments and friable plaques can lead to malapposition and distal embolization with increased major adverse cardiac event (MACE) rates. Methods. 107 patients with a total of 130 SVG interventions were separated into two groups according to either SExS (n = 51) or BExS (n = 56) treatment. Primary endpoint was the MACE rate, which is defined as the composite of cardiac death, myocardial infarction (MI), target vessel (TVR), and target lesion revascularization (TLR) at 30 days and at one-year follow-up. Results. Both patient groups did not differ significantly regarding patient characteristics. The patient outcome was significantly better in the SExS patient group: the MACE rate at 30 days was 1/51 (2.0%) in group SExS vs. 7/56 (12.5%) in group BExS;

p
<
0.05

. At one-year follow-up, the MACE rate remained significantly lower in the SExS group 8/51(15.7%) vs. 20/56 (35.7%) in the BExS group,

p
<
0.02

. Additionally, cardiac death occurred significantly later within the SExS patient group compared to the BExS group (

p
<
0.05

). A better overall outcome of patients with de novo SVG-stenosis compared to patients with previous CABG (coronary artery bypass graft) intervention was noted in both groups. Conclusion. Our findings demonstrate that SVG treatment with SExS is safe and provides clinical benefits by comparatively improving short and especially long-term patient outcomes.
Supplementary Table S1 from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clamby Eric T. , Keith Robert L. , Tennis Meredith A.
Published: April 2023

Supplementary Table S1 lists targets in the dot blots for Figures 3D and 4C.
Supplementary Figure S5 from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clamby Eric T. , Keith Robert L. , Tennis Meredith A.
Published: April 2023

Supplementary Figure S5 shows a representative immunofluorescence image for Figure 5.
Supplementary Figure S3 from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clamby Eric T. , Keith Robert L. , Tennis Meredith A.
Published: April 2023

Supplementary Figure S3 shows a representative immunofluorescence image for Figure 5.
Supplementary Figure S1 from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clamby Eric T. , Keith Robert L. , Tennis Meredith A.
Published: April 2023

Supplementary Figure S1 shows a dot blot for Figure 3D.
Data from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clamby Eric T. , Keith Robert L. , Tennis Meredith A.
Published: April 2023

Abstract
Lung cancer chemoprevention is critical to addressing cancer burden in high-risk populations. Chemoprevention clinical trials rely on data from preclinical models; however, in vivo studies have high financial, technical, and staffing requirements. Precision cut lung slices (PCLS) provide an ex vivo model that maintains the structure and function of native tissues. This model can be used for mechanistic investigations and drug screenings and reduces the number of animals and time required to test hypotheses compared with in vivo studies. We tested the use of PCLS for chemoprevention studies, demonstrating recapitulation of in vivo models. Treatment of PCLS with the PPARγ agonizing chemoprevention agent iloprost produced similar effects on gene expression and downstream signaling as in vivo models. This occurred in both wild-type tissue and Frizzled 9 knockout tissue, a transmembrane receptor required for iloprost's preventive activity. We explored new areas of iloprost mechanisms by measuring immune and inflammation markers in PCLS tissue and media, and immune cell presence with immunofluorescence. To demonstrate the potential for drug screening, we treated PCLS with additional lung cancer chemoprevention agents and confirmed activity markers in culture. PCLS offers an intermediate step for chemoprevention research between in vitro and in vivo models that can facilitate drug screening prior to in vivo studies and support mechanistic studies with more relevant tissue environments and functions than in vitro models.
Prevention Relevance:
PCLS could be a new model for premalignancy and chemoprevention research, and this work evaluates the model with tissue from prevention-relevant genetic and carcinogen exposed in vivo mouse models, in addition to evaluating chemoprevention agents.
Suppl. Table 5 from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: April 2023

PARP signaling and inflammation in cancer
Ninety‐Day Stroke or Transient Ischemic Attack Recurrence in Patients Prescribed Anticoagulation in the Emergency Department With Atrial Fibrillation and a New Transient Ischemic Attack or Minor Stroke
Authors: Wilson Graham , Sharma Mukul , Eagles Debra , Nemnom Marie‐Joe , Sivilotti Marco L. A. , Émond Marcel , Stiell Ian G. , Stotts Grant , Lee Jacques , Worster Andrew , Morris Judy , Cheung Ka Wai , Jin Albert Y. , Oczkowski Wieslaw J. , Sahlas Demetrios J. , Murray Heather E. , Mackey Ariane , Verreault Steve , Camden Marie Christine , Yip Samuel , Teal Philip , Gladstone David J. , Boulos Mark I. , Chagnon Nicolas , Shouldice Elizabeth , Atzema Clare , Slaoui Tarik , Teitlebaum Jeanne , Wells George A. , Nath Avik , Perry Jeffrey J.
Published: April 2023

Background

For patients with atrial fibrillation seen in the emergency department (ED) following a transient ischemic attack (TIA) or minor stroke, the impact of initiating oral anticoagulation immediately rather than deferring the decision to outpatient follow‐up is unknown.

Methods and Results

We conducted a planned secondary data analysis of a prospective cohort of 11 507 adults in 13 Canadian EDs between 2006 and 2018. Patients were eligible if they were aged 18 years or older, with a final diagnosis of TIA or minor stroke with previously documented or newly diagnosed atrial fibrillation. The primary outcome was subsequent stroke, recurrent TIA, or all‐cause mortality within 90 days of the index TIA diagnosis. Secondary outcomes included stroke, recurrent TIA, or death and rates of major bleeding. Of 11 507 subjects with TIA/minor stroke, atrial fibrillation was identified in 11.2% (1286, mean age, 77.3 [SD 11.1] years, 52.4% male). Over half (699; 54.4%) were already taking anticoagulation, 89 (6.9%) were newly prescribed anticoagulation in the ED. By 90 days, 4.0% of the atrial fibrillation cohort had experienced a subsequent stroke, 6.5% subsequent TIA, and 2.6% died. Results of a multivariable logistic regression indicate no association between prescribed anticoagulation in the ED and these 90‐day outcomes (composite odds ratio, 1.37 [95% CI, 0.74–2.52]). Major bleeding was found in 5 patients, none of whom were in the ED‐initiated anticoagulation group.

Conclusions

Initiating oral anticoagulation in the ED following new TIA was not associated with lower recurrence rates of neurovascular events or all‐cause mortality in patients with atrial fibrillation.
Five‐Year Hospital Readmission After Coronary Artery Bypass Surgery and the Association With Off‐Pump Surgery and Sex
Authors: Dimagli Arnaldo , Gaudino Mario , An Kevin R. , Olaria Roberto Perezgrovas , Soletti Giovanni Jr , Cancelli Gianmarco , Harik Lamia , Noiseux Nicolas , Stevens Louis‐Mathieu , Lamy André ,   the CORONARY investigators
Published: April 2023

Background

Limited data exist on long‐term readmission and its association with patient and procedural characteristics after coronary artery bypass grafting. We aimed to investigate 5‐year readmission after coronary artery bypass grafting and specifically focus on the role of sex and off‐pump surgery.

Methods and Results

We performed a post hoc analysis of the CORONARY (Coronary Artery Bypass Grafting [CABG] Off or On Pump Revascularization) trial, involving 4623 patients. The primary outcome was all‐cause readmission, and the secondary outcome was cardiac readmission. Cox models were used to investigate the association of outcomes with sex and off‐pump surgery. Hazard function for sex was studied over time using a flexible, fully parametric model, and time‐segmented analyses were performed accordingly. Rho coefficient was calculated for the correlation between readmission and long‐term mortality.

Median follow‐up was 4.4 years (interquartile range, 2.9–5.4 years). The cumulative incidence rates of all‐cause and cardiac readmission were 29.4% and 8.2% at 5 years, respectively. Off‐pump surgery was not associated with either all‐cause or cardiac readmission. The hazard for all‐cause readmission in women over time was constantly higher than the hazard for men (hazard ratio [HR], 1.21 [95% CI, 1.04–1.40];
P
=0.011). Time‐segmented analyses confirmed the higher risk for all‐cause (HR, 1.21 [95% CI, 1.05–1.40];
P
<0.001) and cardiac (HR, 1.26 [95% CI, 1.03–1.69];
P
=0.033) readmission in women after the first 3 years of follow‐up. All‐cause readmission was strongly correlated with long‐term all‐cause mortality (Rho, 0.60 [95% CI, 0.48–0.66]), whereas cardiac readmission was strongly correlated with long‐term cardiovascular mortality (Rho, 0.60 [95% CI, 0.13–0.86]).

Conclusions

Readmission rates are substantial at 5 years after coronary artery bypass grafting and are higher in women but not with off‐pump surgery.

Registration

URL:
http://www.clinicaltrials.gov/
; Unique identifier: NCT00463294.
No deal: German researchers’ publishing and citing behaviors after Big Deal negotiations with Elsevier
Authors: Fraser Nicholas , Hobert Anne , Jahn Najko , Mayr Philipp , Peters Isabella
Published: April 2023

In 2014, a union of German research organizations established Projekt DEAL, a national-level project to negotiate licensing agreements with large scientific publishers. Negotiations between DEAL and Elsevier began in 2016, and broke down without a successful agreement in 2018; during this time, around 200 German research institutions canceled their license agreements with Elsevier, leading Elsevier to restrict journal access at those institutions. We investigated the effect on researchers’ publishing and citing behaviors from a bibliometric perspective, using a data set of ∼400,000 articles published by researchers at DEAL institutions during 2012–2020. We further investigated these effects with respect to the timing of contract cancellations, research disciplines, collaboration patterns, and article open-access status. We find evidence for a decrease in Elsevier’s market share of articles from DEAL institutions, with the largest year-on-year market share decreases occurring from 2018 to 2020 following the implementation of access restrictions. We also observe year-on-year decreases in the proportion of citations, although the decrease is smaller. We conclude that negotiations with Elsevier and access restrictions have led to some reduced willingness to publish in Elsevier journals, but that researchers are not strongly affected in their ability to cite Elsevier articles, implying that researchers use other methods to access scientific literature.
Bone Marrow Mesenchymal Stem Cell Modified with A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1 Inhibitor Regulates Myocardial Fibrosis in Myocarditis
Authors: Yuan Kexin , Qi Peng , Hao Xiao , Hao Qingqing , Zhao Pei
Published: April 2023

This study assesses the mechanism of BMSC modified with ADAMTS-1 inhibitor in regulating the myocardial fibrosis in myocarditis through TGFβ1/MMP9/TIMP1 pathway and collagen metabolism. Model of viral myocarditis (VMC) rats was established and then assigned into control
set, carrier set, inhibitor set and carrier and inhibitor set randomly followed by analysis of CVF% in atrial tissue, ADAMTS-1 level by RT-PCR and TGFβ1, MMP9 and TIMP1 level by IHC. ADAMTS-1 mRNA level in control set was highest and lowest in inhibitor set. There was fibrosis
in every set inordinately. The degree of myocardial fibrosis was reduced in inhibitor set and carrier and inhibitor set. The quantity of inflammatory cells was also reduced significantly. There was no or sporadic mall focal necrosis. The level of TGFβ1, MMP9 and TIMP1 in the treated
three sets was significant decreased compared with control set with more significant changes in the inhibitor set and carrier and inhibitor set. Collagen metabolism in VMC rats was restrained by BMSC modified with ADAMTS-1 inhibitor and therefore the myocardial fibrosis was ameliorated with
the possible mechanism being through regulation of the TGFβ1/MMP9/TIMP1 signaling pathway.
Bone Marrow Mesenchymal Stem Cells Inhibits Inflammation and Promotes Chondrocyte Activity in Knee Arthritis Rats
Authors: Huang Hua , Zhu Ya , Li Sining
Published: April 2023

This study intends to assess whether BMSCs inhibits inflammation and promotes chondrocyte activity in knee arthritis. 36 SD rats were randomly assigned into group H, group K, group M and group B. The rat models of knee arthritis were established in Group K, group M and group B. After modeling, BMSCs were infused into rats in group B and methotrexate to rats in group M for 6 weeks followed by analysis of TNF-α, IL-6 and IL-1 levels, morphology of knee cartilage, chondrocyte activity and the expression of NO, ERαand cGMP protein. H&E staining found that the surface of knee cartilage in group H was smooth and the morphology of chondrocytes was normal. In group K, bone fissure was formed on articular cartilage surface, and the hyperplasia of deep cells was disorder. The surface of articular cartilage in group B and M gradually became smooth. Compared to group H, TNF-α, IL-6 and IL-1 levels in group K were increased (P< 0.05); their levels in group M and group B were decreased relative to K group (P< 0.05). Compared to group K, chondrocytes activity in groups H, M and B was increased (P< 0.05). NO, ERαand cGMP levels were decreased in knee cartilage of group K relative to H group (P< 0.05) and increased in group M and group B (P< 0.05). In conclusion, BMSCs can down-regulate IL-6, IL-1 and TNF-α, enhance chondrocytes activity, and up-regulate the levels of NO, ERαand cGMP, thus providing a new idea for treating knee arthritis.
miR-663-Containing Exosomes Secreted by Bone Marrow Mesenchymal Stem Cells Ameliorate Cardiomyocyte Oxidative Damage
Authors: Xia Xiaoli , Xu Baoan
Published: April 2023

This study assesses the role of miR-663 in the oxidative damage in myocardial cells through regulating BMSC from exosome. BMSC from rats was cultivated and transfected with miR-663 mimics to measure miR-663 level, BMSC proliferation and apoptosis and cTnT level. Exosome in supernatant
was collected. The myocardial cells were assigned into control set, damage set and exo-miR-663-BMSC set followed by analysis of cell proliferative and apoptotic activity, miR-663 level, ROS, MDA, SOD and GSH-Px content as well as the expression of Nrf2, keap1 and HO-1. BMSC proliferation was
prompted and apoptosis was restrained by miR-663 mimics and BMSC was prompted to be differentiated into myocardial cells. The target gene of miR-663 was keap1. Exo-miR-663-BMSC set showed increased myocardial cell proliferation and decreased apoptosis, reduced ROS and MDA as well as increased
SOD and GSH-Px level along with downregulation of keap1 and upregulated of Nrf2 and HO-1. In addition, the recovery of heart injury caused by IRI was significantly prompted by exo-miR-663-BMSC. In conclusion, exo-miR-663 BMSC is capable to ameliorate heart injury induced by IRI.
Chordin-Like 1 Regulates Bone Marrow Stem Cell Proliferation and Excretion of Exosome and Myocardial Damage Under High Sugar
Authors: Zhang Hongbo , Tao Liang , Zhang Xinrui , Zhang Hongyan
Published: April 2023

This study assesses the role of CHRDL1 (Chordin-like 1) i in the bone marrow stromal cells (BMSC) proliferation and excretion of exosome and myocardial damage under high sugar. BMSC from rats with high CHRDL1 expression was established. The exosome in the supernatant of BMSC with high CHRDL1 level was collected. H9C2 cells were assigned into control set, high sugar set and exo-CHRDL1-BMSC set followed by analysis of CHRDL1 level, BMSC proliferation and apoptosis, expression of Beclin-1, Atg5, Bcl-2 and Bax, and ROS and SOD activity. Cell proliferation was prompted and apoptotic activity was reduced in exo-CHRDL1-BMSC set with reduced ROS activity and increased SOD activity as well as upregulated Bcl-2 and downregulated Bax. In addition, exo-CHRDL1-BMSC set presented increased CHRDL1 secretion and upregulated Beclin-1 and Atg5 expression. In conclusion, proliferation of BMSC under high sugar is prompted and apoptosis is reduced by CHRDL1 through regulating the autophagy.
Identification of Key Genes Involved in Glioblastoma by Integrated Bioinformatics Analysis
Authors: Yan Dongke , Gong Yanchao , Wang Yongling , Li Longmei , Tong Wenhui , Pang Jingjie
Published: April 2023

Glioblastoma (GBM) is the most frequently identified malignancy of the brain. Due to the special tumor location, it is extremely urgent to explore key genes involved in the pathogenesis of GBM. In this study, we tried to identify vital genes that participate in the GBM progression by
analyzing TCGA-sourced transcriptome data and identified 3183 differentially expressed genes (DEGs). Meanwhile, we also observed that CRYGN, MICAL2, BICDL1, PLK2, MTHFD2, OSMR, COL22A1, MSTN, and G0S2 expressions were significantly associated with patients’ survival. Immune infiltration
analysis indicated that eight genes enhanced the immune infiltration in GBM, while BICDL1 had no significant effect. In conclusion, our study demonstrates that the eight genes are potential key genes involved in GBM and significantly connected to patients’ prognosis.
Irisin Ameliorates Cerebral Vasospasm and Early Brain Injury in Rats with Experimental Subarachnoid Hemorrhage
Authors: Liu Zhumin , Lei Dan
Published: April 2023

Irisin is a cytokine mainly secreted by skeletal muscles, widely distributed in the body with functions of anti-oxidation, anti-inflammation, prevention of reperfusion injury, immune stimulation, and reduction of cerebral infarction. In this study, rats with subarachnoid hemorrhage
(SAH) were used as experimental subjects, and irisin was injected intraperitoneally to investigate irisin’s effect on cerebral vasospasm and early brain injury (EBI). After establishment of the animal model of SAH, animals were administered with irisin through intraperitoneal injection.
The animal tissues were taken out to assess the morphological changes, and neurons apoptosis by TUNEL staining and Nissl staining. Brain edema score was used to assess the severity of brain injury, and the relationship between related signal pathways was detected by Western blot. Administration
of irisin significantly reduced cerebral vasospasm and decreased neuronal apoptosis induced by SAH. Irisin inhibited the apoptosis of prefrontal cortex mitochondrial neurons, and decreased Bax/Bcl-2 and cytochrome C in the cytoplasm. The expressions of PSD-95 and GAP-43 and BDNF in brain tissues
were decreased upon SAH, but their expressions were partially restored after treatment with irisin. Irisin decreases neuronal apoptosis and mitochondrial function with up-regulation of synapse proteins, thereby exerting a protective effect on EBI and SAH.
The Influence of Zoledronic Acid on the Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells and Tibial Fracture in Rats via Phosphatidylinositol-3-Kinase/AKT Pathway
Authors: Liu JianZhou , Wang Hao , Shang GuoJun , Lv XiangYang , Xu ZhenWei , Xiong FuJun
Published: April 2023

Fracture healing is an extremely complex physiological process, involving a sequence of crucial mechanisms. Whether zoledronic acid (ZA) affects proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and tibial fractures still remains unknown. We
performed construction of the tibial fracture model in rats and analyzed the impact of ZA and ZA+LY294002 on fracture healing in rats. Test of the influence of ZA and ZA+LY294002 on crucial osteogenic genes alkaline phosphatase (ALP), RUNX2, OCN and OPN was performed. Examination of the influence
of suppressing the PI3K/AKT pathway on the proliferation with bone differentiation of ZA. Results showed ZA distinctly accelerated the proliferation and ALP activity of BMSC cells, BMP2, RUNX2, OCN, OPN and the activation of the PI3K/AKT pathway. Repression of PI3K/AKT pathway suppressed the
proliferation and osteogenic differentiation action of ZA. ZA boosted tibial fracture healing in rats via activating the PI3K/AKT pathway. ZA facilitates the proliferation with osteogenic differentiation of BMSC cells and tibial fracture healing in rats via activating the PI3K/AKT pathway.
Paeonol Effects on Repair of Cerebral Cortex Injury and the Expression of Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B in Postnatal Rats with Cerebral Palsy
Authors: Chen Lu-lu , Su Feng , Li Si-nan , Yi Xin , Luo Yuan-yuan , Liang Dong , Tang Zhen-chuan , Feng Chao , Cheng Kai , Deng Fang
Published: April 2023

Objective: To observe Paeonol effects on repair of cerebral cortex in young rats with CP. Methods: Dividing CP model rats as Model and Pae groups, and a sham operation control group was set up. Using Nissl staining to evaluate morphology and number of cortical neurons
in young rats, and to determine the protein of BDNF/TrkB in peripheral serum and cerebral cortex. Results: The number of normal morphological neurons in cerebral cortex of young rats in Pae group were more than that of Model group (P < 0.01). BDNF and TrkB concentrations were
significantly up-regulation in serum in Model and Pae groups (P < 0.001), meanwhile, The BDNF and TrkB concentrations significantly up-regulated in serum in Pae group (P < 0.01). By IHC and WB assay, BDNF and TrkB protein levels were significantly up-regulation in serum
in Model and Pae groups (P < 0.001), meanwhile, The BDNF and TrkB protein levels were significantly up-regulation in serum in Pae group (P < 0.01). Conclusion: Pae can all play a role in repairing cerebral cortex damage in young rats with cerebral palsy via BDNF/TrkB.
Unilamellar Characteristic Analysis of 1,2-dioleoyl-sn-3-phosphocholine Liposome of Various Sizes via Atomic Force Microscopy and Patch-Clamp
Authors: Lee Chi Hyung , Kwak Jong Hyeok , Sung Soon Ki , Lee Sang Weon , Kwak Jinsung , Kim Kyung-wan , Kang Hyo Seok , Kim Gyeong Rip
Published: April 2023

DOPC liposome properties of various sizes were analyzed via atomic force microscopy (AFM) and patch-clamp. The unilamellarity of small DOPC liposome (below 1 μm) was confirmed via Cryogenic transmission electron microscopy (Cryo-TEM). Small DOPC liposome (below 1 μm)
showed a bending modulus (kbend) ranging (between 10−18 and 10−20 J). The bending modulus value was a size dependence. In order words, it decreased as DOPC liposome size increased. For DOPC liposome (above 1 μm), patch-clamp was
used to achieve electrically tight whole-cell configurations. Our result showed that the unilamellar DOPC liposome (above 1 μm) exhibit RC circuit response property. It was similar to theoretical values (τ = 4.52 ms) of the unilamellar liposome. In this study, the uniform
lamellarity of the DOPC liposome of various sizes was confirmed through electrical and mechanical properties of DOPC liposome.
Antioxidant and anti-inflammatory properties of pine pollen extract promote wound healing
Authors: Zhou Conglai , Yang Qiming , Chen Long , Fang Kaiyun , Lu Xiaolong , Song Xiongbo , Sun Li
Published: April 2023

Wound healing is a complex cascade reaction process which is frequently delayed or non-healed due to oxidative stress and persistent inflammation. As a natural antioxidant, pine pollen has potential antioxidant and anti-inflammatory benefits. In this study, we demonstrated that pine
pollen extract can promote collagen formation, angiogenesis, granulation tissue and hair follicles regeneration, and regulate inflammatory process. Moreover, pine pollen extract performed significantly better than control group in antioxidant and anti-inflammatory features. In addition, the
concentration of 1 mg/mL is more conducive to promote wound healing. These findings indicated that pine pollen extract has high antioxidant and anti-inflammatory activity which could speed up skin tissue regeneration and promote wound healing, being useful in regenerative medicine.
Applications of antioxidant nanoparticles and hydrogels in osteoarthritis: A review
Authors: Chen Junrong , Chen Long , Song Xiongbo , Fang Kaiyun , Sun Li
Published: April 2023

During osteoarthritis, the oxidation-reduction balance will be broken, resulting in the excessive formation of reactive oxygen species. These reactive oxygen species have been shown to disrupt proteins, lipids, and deoxyribonucleic acid. They induce oxidative strain, which can induce
the development of osteoarthritis and lead to worse consequences. To solve this problem, antioxidant molecules have attracted wide attention for their ability to scavenge free radicals and reactive oxygen species. Nevertheless, most antioxidants encounter obstacles that affect their bioavailability,
including a narrow absorption capacity, difficulty in penetrating cell membranes, and disintegration during delivery. Therefore, to solve these problems, the excellently targeted delivery, biocompatibility, deformability, and other characteristics of nanoparticles and hydrogels have been considered,
and nanoparticles and hydrogels are at present being widely developed as antioxidant carriers. Nanoparticles and hydrogels that target the oxidative stress pathway can be mixed with antioxidants to increase their bioavailability, adhesion, and other related characteristics, which leads to
better treatment of osteoarthritis. This research study aims to examine the biological scaffolds of osteoarthritis, which contain antioxidant nanoparticles and antioxidant hydrogels, as well as process controlling reactive oxygen compounds throughout the entire knee joint cavity. In addition,
current challenges and potential solutions that can use antioxidant nanoparticles and antioxidant hydrogel biological scaffolds have been proposed to provide a theoretical basis for their future clinical applications.