bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 655: Protecting The Saphenous Vein Endothelium During Bypass Surgery
Authors: Sedovy Meghan W , Leng Xinyan , Iqbal Farwah , Leaf Melissa , Malek Arya , Wyatt David A , Choate Cynthia W , Rowe Joseph F , Baker Joseph W , Johnstone Scott R , Joseph Mark
Published: October 2023

Coronary artery bypass graft surgeries commonly use saphenous vein grafts to revascularize diseased coronary arteries. Despite surgical and pharmacological advancements, graft failure rates remain high. Loss of endothelial cells (EC) during saphenous vein harvest and preservation likely contributes to the high incidence of graft failure. Standard methods of saphenous vein preparation and preservation during surgery include perfusion with heparinized saline solutions, a practice known to induce EC damage. As such, improved methods of saphenous vein storage may be the key to preserving EC and reducing graft failure rates. Here, we assessed the hypothesis that maintaining saphenous veins in autologous heparinized blood would preserve EC coverage and reduce cellular damage compared to standard of care, heparinized saline. To investigate this, saphenous vein tissues from 12 patients undergoing coronary artery bypass graft surgery were split into 2 treatment groups, 1) standard maintenance in heparin-saline (n=6) and 2) maintenance in heparin-blood (n=6). At the end of the surgeries, excess saphenous vein tissues were immediately fixed in 4% PFA to analyze endothelial coverage and DNA damage. In heparin-saline veins, histological analysis by H&E and Movat pentachrome staining revealed a broken or absent luminal layer and exposed lamina matrix, suggesting a loss of endothelial cell coverage. Luminal cell coverage was notably increased in heparin-blood samples. Immunofluorescent staining of endothelial markers VE-cadherin and endothelial nitric oxide identified a significant improvement in endothelial coverage in the heparin-blood group compared to heparin-saline. To determine the health of remaining endothelial cells, DNA damage was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Our data show that most of the endothelium (VE-cadherin positive) in heparin-saline tissues was TUNEL positive compared with heparin-blood. In conclusion, our data indicate that maintaining saphenous vein tissues in solutions containing autologous heparinized blood helps preserve the endothelium and maintains vein graft health which has the potential to improve vein graft patency rates in patients.
Abstract 656: Spatiotemporal Transcriptomics Analysis Of Central Venous Stenosis Suggests TNF-alpha As A Potential Therapeutic Target In Chronic Kidney Disease Rats
Authors: Lotfollahzadeh Saran , Shafiq Esha , Elzinad Najla , Chitalia Vipul
Published: October 2023

Introduction:
In the United States, 50-80% of chronic kidney disease (CKD) patients use a central venous catheter (CVC) for hemodialysis. Protracted exposure of CVCs against fragile venous walls results in central venous stenosis (CVS), which has devastating complications. Despite its higher prevalence of up to 40% in CKD patients, little is known about its pathogenesis and the means to target it.

Hypothesis:
We posit that a venous guide-wire injury will induce specific perturbation of genetic pathways in the CKD milieu.

Methods:
A group of twenty-two 8-12-week-old Sprague Dawley rats on 0.75 % Adenine diet (CKD rats) for two weeks and N=18 normal chaw (control ) were subjected to guide wire injury on their right internal jugular veins. Animals were harvested on days 0, 5, and 14 after the injury. GeoMax Whole transcriptome analysis was performed after validation studies.

Results:
Compared to non-CKD rats, injured veins of CKD rats showed higher thrombus, deposition of extracellular matrix, and perivascular fibrosis, all consistent with CVS. Spatial transcriptomics analysis revealed significant (P < 0.05) and at least more than 50% upregulation of genes of matrix modifying enzymes (MMP 10 and 19), collagen, Notch (Notch3, Jag1), Wnt (Fad4, Axin1, Wnt11b), and Hedgehog (Gli1, Kif7, Ihh) pathways. OF these changes, a consistent 1.6 to 2-fold upregulation was noted in the Tumor necrosis factor (TNF) family members (Tnfrsf1b, Traf3, ifnb1, Tradd) in endothelial and vascular smooth muscle cells. This finding was validated using IHC, which demonstrated TNF-alpha upregulation in the endothelial cells of the injured veins of CKD rats (P= 0.002, P <0.0001 at days 5 and 14) compared to controls. Mechanistic probing revealed that endothelial cells exposed to the serum from CKD patients affected survival and migration (P <0.05), both of which were reversed by anti-TNF neutralizing antibodies (P =0.05).

Conclusion:
Leveraging a rodent model of CVS, this study demonstrates higher perivascular fibrosis and thrombus formation in CKD rats. This is the first study examining the spatiotemporal genetic perturbation in the injured vein of CKD rats showing the multitude of pathways perturbed by the injury in the CKD milieu, some of which can be therapeutically targeted.
Abstract 658: Endothelial And Smooth Muscle Cell Interaction In The Maintenance Of Pathological Muscularization In Pulmonary Hypertension
Authors: Saddouk Fatima Zahra , kuzemczak Andrew , Saito Junichi , Greif Daniel
Published: October 2023

Excess smooth muscle cell (SMC) accumulation characterizes cardiovascular diseases and is highly studied; however, once established, mechanisms underlying maintenance of hypermuscularization are poorly delineated. Herein, we investigate maintenance of SMCs coating normally unmuscularized distal pulmonary arterioles in chronic hypoxia-mediated pulmonary hypertension (PH), and reversal of this pathology with re-normoxia. With hypoxia in mice or culture, lung endothelial cells (ECs) upregulate hypoxia-inducible factor (Hif)-1a and 2a which induce platelet-derived growth factor-B (PDGF-B), and these factors reduce to normoxic levels with re-normoxia. EC HIFα over-expression during re-normoxia prevents reversal of distal muscularization and PH. Moreover, after establishment of hypoxia-induced distal muscularization and PH, EC-specific deletion of
Hif1a
,
Hif2a
or
Pdgfb
reverses these effects. In human idiopathic pulmonary artery hypertension, HIF1A, HIF2A, PDGFB and autophagy-mediating gene products, including Beclin1, are upregulated in pulmonary artery SMCs and/or lung lysates. Furthermore, in mice, hypoxia-induced EC-derived PDGF-B upregulates Beclin1 in distal arteriole SMCs, and after distal muscularization is established, re-normoxia, EC
Pdgfb
deletion or treatment with STI571 (which inhibits PDGF receptors) downregulates SMC Beclin1 and other autophagy products. Finally, SMC-specific
Becn1
deletion reverses distal muscularization and PH by inducing apoptosis. Thus, chronic hypoxia induction of HIFα-to-PDGF-B axis in ECs is required for non-cell autonomous Beclin1-mediated survival of pathological distal arteriole SMCs.
Abstract 663: Smooth Muscle Cell-specific MMP-3 Deletion Reduces Osteogenic Transformation And Medial Artery Calcification
Authors: Xie Yangzhouyun , Lin Tonghui , Berezowitz Alexa , Wang Xue-Lin , Cai Yujun , Guzman Raul J
Published: October 2023

Objective:
Vascular calcification is highly prevalent in atherosclerosis, diabetes, and chronic kidney disease. It is associated with increased morbidity and mortality in patients with cardiovascular disease. Matrix metalloproteinase 3 (MMP-3), also known as stromelysin-1, is part of the large matrix metalloproteinase family. It can degrade extracellular matrix components of the arterial wall including elastin, which plays a central role in medial calcification. In this study, we sought to determine the role of MMP-3 in medial calcification.

Methods and Results:
We found that MMP-3 expression was increased in vascular smooth muscle cells (SMCs) cultured in a phosphate calcification medium. It was also highly expressed in the calcified tibial arteries in patients with peripheral arterial disease (PAD). Knockdown and inhibition of MMP-3 suppressed phosphate-induced SMC osteogenic transformation and calcification, whereas the addition of a recombinant MMP-3 protein facilitated SMC calcification. In an
ex vivo
organ culture model and a rodent model of medial calcification induced by vitamin D
3
, we found that MMP-3 deficiency significantly suppressed aortic medial calcification. We further found that medial calcification and osteogenic transformation were significantly reduced in SMC-specific MMP-3-deficient mice, suggesting that MMP-3 in SMCs is crucial for medial calcification.

Conclusion:
These findings suggest that MMP-3 expression in vascular SMCs is an important regulator of medial calcification and that targeting MMP-3 could provide a therapeutic strategy to reduce it and address its consequences in patients with PAD.
Abstract 665: The Proangiogenic Effect Of Extracellular Camp Through Notch Independent Mechanism
Authors: Xu Jasmine , Wang Shumin , Zhang Yishuai , Yan Chen
Published: October 2023

Ischemic heart disease (IHD) caused by atherosclerosis is the leading cause of death globally. Blood clots formed after the rupture of atherosclerotic plaques can cause complete blockage of the coronary artery, leading to myocardial infarction (MI) and even death. Promoting
angiogenesis
and restoring blood flow in the infarcted area is crucial for the repair of myocardial injury. Therefore, developing a safe, effective pro-angiogenic drug is urgently needed. Adenosine 3',5'-cyclic monophosphate (cAMP) is a cyclic nucleotide that acts as a key intracellular second messenger in numerous signal transduction pathways and regulates various cellular functions, including cell growth and differentiation, gene transcription and protein expression. Studies have shown that the extracellular cAMP (ex-cAMP) has been identified in several cell and tissue types, including the heart. The infusion of cAMP averted myocardial hypertrophy and fibrosis in a mouse heart failure model. Therefore, we hypothesize that ex-cAMP has proangiogenic effects in human endothelial cells. To test our hypothesis, we treated human umbilical vein endothelial cells (HUVEC) with cAMP (not able to cross the cell membrane) to determine the effects of ex-cAMP on EC proliferation, survival, migration, and angiogenesis using MTT, Brdu incorporation assay, wound scratch and tube formation. We found that ex-cAMP significantly increased HUVEC proliferation indicated by enhanced proliferation rate and Brdu incorporation. However, ex-cAMP has no effect on H
2
O
2
-induced EC death. ex-cAMP increased HUVEC migration by 30%. Importantly, ex-cAMP promoted robust tube formation (about 50%). Using western blot, we examined the role of ex-cAMP in the changes of Delta like 4-Notch signaling which is an essential signaling pathway for sprouting angiogenesis. Surprisingly, we did not observe any changes of Notch ligands (Dll4 and Jag1) and Notch1 receptor expression and activation. In conclusion, ex-cAMP demonstrated proangiogenic effects on HUVEC and these effects are Notch independent. Our findings shed light on the ex-cAMP as a potential potent therapeutical proangiogenetic drug that is safe, inexpensive, and stable.
Abstract 672: Disrupted Interaction Between Neutrophils And Regulatory T-cells In Patients With Coronary Artery Disease
Authors: Schneider Maike , Skoglund Camilla , Lundberg Anna , Chung Rosanna W , Jonasson Lena
Published: October 2023

Many patients with coronary artery disease (CAD) suffer from low-grade chronic inflammation indicating an increased risk of recurrent cardiac events. The inflammatory state in CAD has been associated with elevated neutrophil counts, but also with a deficiency of regulatory T-cells (T
regs
). The role of T
regs
in the regulation of neutrophil survival has been proposed recently. Here, we hypothesised that the interaction between T
regs
and neutrophils might be altered in CAD patients, and specifically investigated the impact of T
regs
on neutrophil apoptosis. Blood was collected from 20 CAD patients (mean age 65, 50% female) and 19 controls (mean age 64, 53% female). Neutrophils and T
regs
were isolated by density gradient centrifugation. Autologous neutrophils and T
regs
were then cocultured at ratios 1:0, 10:1, 4:1 and 1:1 for 5 h. Apoptosis (Annexin V + SYTOX staining) of neutrophils was assessed by flow cytometry. In controls, neutrophils showed increased apoptosis in a dose-dependent manner (p=0.005) when co-cultured with T
regs
(Figure 1A). Neutrophil apoptosis was significantly lower in patients than in controls at all ratios, (1:0, 10:1, 4:1, p< 0.05, and 1:1, p=0.01). Moreover, T
regs
did not affect neutrophil apoptosis in patients at any ratio (Figure 1B). To conclude, neutrophils from CAD patients were less prone to apoptosis compared to neutrophils from controls. T
regs
from patients were also less capable of inducing neutrophil apoptosis. Disrupted interaction between neutrophils and T
regs
may be a driving force of chronic inflammation in CAD patients.
Abstract 682: Incorporation Of Phosphatidylserine Enhanced Anti-inflammatory Effects Of Synthetic High Density Lipoproteins
Authors: Yu Minzhi , Dorsey Kristen H , Schwendeman Anna
Published: October 2023

Objective:
Phosphatidylserine (PS) is an anionic, bioactive phospholipid component in endogenous high-density lipoprotein (HDL). The PS content in HDL has been found to be positively correlated with various HDL functions including cholesterol efflux and anti-inflammation effects. It has been hypothesized that introducing PS to synthetic HDL (sHDLs) could enhance the therapeutic effects of sHDLs. To test this hypothesis, the effects of PS on particle characteristics, anti-inflammatory effects,
in vitro
and
in vivo
cholesterol efflux capacities, and pharmacokinetic profiles of sHDLs were investigated in the present study.

Methods:
sHDLs composed of ApoA-1 mimetic peptide 22A, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine (POPS) were prepared using the lyophilization-rehydration method. The anti-inflammatory effects of different sHDLs were investigated on LPS-treated RAW 264.7 macrophages and HUVEC cells. The
in vitro
cholesterol efflux effects of sHDLs were evaluated on [
3
H] cholesterol-laden J774 cells. For
in vivo
studies, sHDLs containing different POPS contents were injected into Sprague-Dawley rats through the tail vein. The serum concentrations of phospholipids, total cholesterol, and free cholesterol at different time points were quantified.

Results:
sHDL with different PS contents presented similar particle sizes, while sHDLs containing higher PS contents showed greater particle stability. No statistical difference in
in vitro
cholesterol efflux capacity was observed among sHDLs with different PS contents. On LPS-treated macrophages and endothelial cells, PS-containing sHDLs inhibited the production of pro-inflammatory cytokines to a greater extent compared to PC-sHDLs. PS-containing sHDLs showed slightly higher cholesterol mobilization effects at early time points
in vivo
. However, no difference was found in the pharmacokinetic profiles between different sHDLs.

Conclusions:
Incorporating anionic phosphatidylserine into sHDL particles significantly increased their anti-inflammatory effects while not greatly affecting the cholesterol efflux capacity and pharmacokinetic profiles of sHDLs.
Abstract 697: Gene Co-expression And Meta-analysis Of Human Coronary Artery Disease Identified A Novel Mechanism Of Macrophage Activation Through Lncrna SPANXA2-OT1/mir-338/IL-8 Triad
Authors: Jha Prabhash K , Itto Lucas Y , Vijay Aatira , Becker-Greene Dakota , Sonawane Abhijeet , Lupieri Adrien , Aikawa Elena , Uchida Shizuka , Aikawa Masanori
Published: October 2023

Background:
Coronary artery disease (CAD) remains the leading cause of mortality worldwide. Although long noncoding RNAs (lncRNAs) do not translate into protein, they interact with DNA, RNA, miRNA, and proteins. lncRNAs thus are interesting therapeutic targets. lncRNAs act as miRNA sponges by sequestering miRNA molecules, which in turn suppress miRNA activity, resulting in consequent increases in the levels of miRNA target genes. But how lncRNAs regulate the pathology of CAD via miRNA sponge formation, however, remain incompletely understood.

Methods:
We performed gene-expression meta-analysis to identify differentially expressed lncRNAs, miRNA and mRNAs in CAD using a comprehensive 4-part analysis pipeline (Fig A). We performed the weighted gene co-expression network analysis (WGCNA) by analyzing GSE40231 dataset to confirm highly correlated lncRNAs and its coding gene partners. Using human primary macrophages we conducted
in vitro
validation of the candidate coding-noncoding RNA regulatory triad.

Results:
Our computational analysis led to 2332 mRNAs, 159 miRNAs and 515 lncRNAs that were significantly higher or lower in human CAD patients as compared to control. WGCNA identified 26 lncRNA-mRNA co-expression modules (Fig B and C). Network prioritization of top co-expression modules identified the lncRNA,
SPANXA-OT1,
as a potential key candidate. In human primary macrophages, luciferase assay established that
SPANXA2-OT1
binds to
miR-338
through its miRNA response elements (Fig D-F). Gain-of-function and loss-of-function experiments revealed that SPANXA2-OT1 and miR-338 regulates the expression of proinflammatory genes, e.g.,
IL-8
, that may contribute to the pathophysiology of CAD (Fig G and H).

Conclusion:
Our results indicate that the lncRNA,
SPANXA2-OT1
, binding to
miR-338
plays an important role in IL-8-mediated inflammation and may provide molecular basis for the identification of novel therapeutic targets for CAD.
Abstract 700: Genetic Deletion Of Neutrophil Elastase Does Not Alter Lesions In Mice With Atherosclerosis Induced By Aav8-mediated Over-expression Of PCSK9
Authors: Macleod Clare , Miguelez-Crespo Allende , Villalobos Elisa , Natalie Homer , Giacca Mauro , Hadoke Patrick , Nixon Mark
Published: October 2023

Introduction:
Elevated circulating glucocorticoids are causally linked to increased cardiovascular disease. Atherosclerosis is a key cardiovascular pathology, yet the contribution of glucocorticoids underlying atherogenesis is unclear. Corticosteroid binding globulin (CBG) regulates glucocorticoid action through binding, thus controlling its systemic bioavailability. Cleavage of CBG by neutrophil elastase (NE) is proposed to enhance bioavailability of glucocorticoids by reducing its binding affinity. Strikingly,
Apoe
-/-
mice lacking NE (ELA
-/-
) display reduced atherosclerosis.

Hypothesis:
This investigation addresses the hypothesis that NE influences atherogenesis through CBG cleavage, increasing glucocorticoid bioavailability at sites of plaque development.

Methods:
Adult (8-12wk old) male C57BL/6J, ELA
-/-
and ELA
+/+
mice were injected with AAV8-PCSK9 (IP; 1x10
12
vector genomes) and fed a western diet (21% fat; 0.21% cholesterol) for 18wks (N=10-13). Control mice received diet without viral injection (N=10).

Results:
In C57BL/6J mice, histological analysis of brachiocephalic arteries demonstrated lesion development with AAV8-PCSK9-treatment, in parallel with increased (P=0.015) circulating NE protein levels (58.0 ± 5.5ng/ml) compared to diet-control mice (NE levels 32.8 ± 6.2ng/ml). AAV8-PCSK9 treatment did not alter circulating glucocorticoids (Corticosterone AM levels P=0.94; AAV8-PCSK9 65 ± 16nM; Control 74 ± 36nM) but hepatic CBG (Serpina6) transcript levels were reduced (1-fold; P=0.01; AAV8-PCSK9 0.57 ± 0.04; Control 1.13 ± 0.20). Interestingly, no differences in lesion size (P=0.8539; 23.2 ± 2.5%) or collagen content (P=0.5156; 17.64 ± 5.6%), or in circulating glucocorticoid levels (corticosterone AM levels; P=0.36; 225 ± 59nM) were observed in ELA
-/-
mice compared to controls (lesion size 24.2 ± 6.3%; collagen 12 ± 5%; glucocorticoid levels 142 ± 29nM).

Conclusions:
In contrast to published data using

Apoe
-/-

mice, these results demonstrate that NE does not influence lesion size in this model of atherosclerosis. This suggests that NE inhibition would not be a useful therapeutic target in atherosclerosis. Future studies will directly address the role of CBG in the development of atherosclerosis.
Abstract 715: Genetically Proxied Inhibition Of L-2-Hydroxyglutarate Dehydrogenase Reduces The Risk Of Coronary Artery Disease: A Mendelian Randomization And Network Medicine Study
Authors: Song Euijun
Published: October 2023

Introduction:
L-2-hydroxyglutarate dehydrogenase (L2HGDH) deletion-induced L-2-hydroxyglutarate accumulation plays a cardioprotective role in hypoxic conditions by eliminating reactive oxygen species. However, there has been no causal evidence in real-world clinical data.

Hypothesis:
We examined the potential therapeutic effects of
L2HGDH
inhibition on coronary artery disease (CAD) using Mendelian randomization (MR) and network medicine analyses.

Methods:
We used nine
L2HGDH
-proxied genetic variants associated with blood 2-hydroxyglutarate levels (6,287 European individuals) as genetic instruments, and performed a two-sample MR analysis using the CARDIoGRAMplusC4D meta-analysis datasets of CAD (60,801 cases and 123,504 controls). A protein-protein interaction network analysis was also performed to determine the potential therapeutic effects of
L2HGDH
inhibition on a CAD disease module.

Results:
Genetically proxied inhibition of
L2HGDH
associated with 2-hydroxyglutarate levels decreased the risk of CAD (odds ratio [OR] 0.486, 95% confidence interval [CI] 0.242-0.977, P=0.043). This potential causal association between
L2HGDH
inhibition and CAD was unlikely to be biased by horizontal pleiotropy. Network proximity analysis showed that L2HGDH is significantly closer to the CAD disease module in the human heart protein-protein interactome (P=0.016).

Conclusions:
In conclusion, our MR and network analyses suggest potential causal and pathobiological associations between genetically proxied inhibition of
L2HGDH
and CAD. Our findings may have therapeutic implications for L2HGDH inhibitors in CAD.
Abstract 721: A Middle-aged Female With Myocardial Infarction In The Setting Of Spontaneous Coronary Artery Dissection
Authors: Petit-Homme Daphne
Published: October 2023

There are myriads of causes of a myocardial infarction (MI), most commonly metabolic syndromes, including hypertension, hypercholesterolemia, and hyperlipemia. Connective tissue disorders are rarely thought of as a factor that can lead to an MI and therefore are commonly missed. A 45-year-old Hispanic female with no reported medical problems presented to the hospital for an 8/10 substernal pressure-like chest pain with associated shortness of breath. She stated that the pain radiated to bilateral arms but was not brought on by exertion nor was it relieved by rest. Blood pressure was 196/104 mmHg at the time of admission. Her physical exam was unremarkable except for extremities showing hyperextensible joints with classic swan neck deformity of the fingers consistent with Ehlers Danlos Syndrome. Her troponin was elevated at 0.867 and a 12-lead EKG showed ST depression and T-wave inversion consistent with Non-ST elevated myocardial infarction. Patient’s coronary angiography was diagnostic for Spontaneous Coronary Artery Dissection (SCAD) of mid-to-distal segment of left anterior descending artery. Although prognosis is very fair with patients who receive prompt treatment, SCAD is often missed because it is an uncommon condition. Many providers are unfamiliar with SCAD and its evidenced based medicine treatment standards. These should include aspirin, beta-blocker, clopidogrel, and angiotensin converting enzyme inhibitor or angiotensin receptor blockers for patients with associated hypertension. Patient with diagnosed SCAD should also undergo vascular imaging and cardiac rehabilitation. The presented patient was also sent for genotyping to evaluate for the connective tissue disorder, Ehlers Danlos Syndrome. In conclusion, it is imperative to recognize and diagnose an MI and investigate the underlying causes, including the uncommon ones like SCAD, quickly and efficiently.
The collection of the genus Mispila Pascoe, 1864 housed in the Natural History Museum, London (Coleoptera: Cerambycidae)
Authors: XIE GUANGLIN , BARCLAY MAXWELL V. L. , WANG WENKAI
Published: October 2023

Data on the collection of the genus Mispila Pascoe, 1864 (Lamiinae, Pteropliini) deposited in the Natural History Museum, London are presented. Mispila (s. str.) auguralis Pascoe, 1878 is removed from synonymy with Mispila (s. str.) venosa Pascoe, 1864 and considered as a subspecies: Mispila (s. str.) venosa auguralis Pascoe, 1878 stat. rev.. Lectotypes are designated for Mispila (s. str.) obscura Gahan, 1890 and Mispila (Dryusa) flexuosa (Pascoe, 1864). The variation of Mispila venosa venosa Pascoe, 1864 is shown. A total of 20 valid species/subspecies are listed.
Organizing for Smart City Development: Research at the crossroads. Introduction to the Special Issue
Authors: Mora Luca , Appio Francesco Paolo , Foss Nicolai J. , Arellano-Gault David , Zhang Xiaoling
Published: October 2023

Worldwide, smart city projects have emerged as a response to urban crisis conditions with the aim of leveraging digital technologies for urban innovation and sustainable development. However, these projects involve complex organizational challenges that have received little attention in existing smart city research, particularly in the exploration of interorganizational collaboration. The disconnect between organization studies and smart city research means that these two knowledge fields have yet to maximize the valuable insights that each one can offer to the other. To address this gap, this Special Issue seeks to foster cross-fertilization. Elaborating on the contributions in our Special Issue, we present potential and actual research crossroads conceptual and theoretical arenas in which collaborative efforts between organization studies and smart city research can thrive. We aim to bridge knowledge gaps and generate mutual benefits by stimulating interdisciplinary encounters. This approach offers opportunities for empirical research that can expand organization studies and their theories while deepening our understanding of organizations, organizing, and the organized in smart city projects, thereby contributing to theoretical and practical advancements.
Surgical Treatment of an Unusual Ski Injury: Combined Tibial Fracture With Anterior Cruciate Ligament Avulsion and Segond Lesion
Authors: Monaco Edoardo , Cavaignac Etienne , Criseo Natale , Annibaldi Alessandro , Cantagalli Matteo , Pucciatti Rita , Carrozzo Alessandro , Feretti Andrea
Published: October 2023

Background:

Alpine skiing is considered to be a high-risk sport due to frequent knee injuries and lower limb fractures. The most common lower limb fracture is tibial shaft fracture, while the most common ligament injuries include anterior cruciate ligament (ACL) or medial collateral ligament tears. An injury rarely described in the literature is the association of a bony leg fracture with an ACL injury and Segond fracture.

Indications:

While the tibial fracture can be managed with intermedullary nailing and proximal ACL tears can be managed with primary repair, the combination of treatments including fixation of the Segond fracture is uncommon.

Technique Description:

We report combination treatment with nailing for the tibial fracture, primary repair for the ACL avulsion, and primary fixation of Segond fracture.

Results:

Simultaneous reduction and fixation of the fracture and stabilization of the knee with ACL and anterolateral ligament repair in a single stage resulted in an excellent outcome with complete healing of tibial fracture, ACL repair, and Segond fixation at final follow-up.

Discussion/Conclusion:

Even if combined leg fracture associated with ipsilateral ACL tear and Segond fracture is a very rare injury, the described technique based on 1-stage fixation of the 3 injuries is a viable option. This surgical technique can be considered a reparative treatment, with the goal of preserving the joint.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
FLARE: a fast and flexible workflow for identifying RNA editing foci
Authors: Kofman Eric , Yee Brian , Medina-Munoz Hugo C. , Yeo Gene W.
Published: October 2023

Background

Fusion of RNA-binding proteins (RBPs) to RNA base-editing enzymes (such as APOBEC1 or ADAR) has emerged as a powerful tool for the discovery of RBP binding sites. However, current methods that analyze sequencing data from RNA-base editing experiments are vulnerable to false positives due to off-target editing, genetic variation and sequencing errors.

Results

We present FLagging Areas of RNA-editing Enrichment (FLARE), a Snakemake-based pipeline that builds on the outputs of the SAILOR edit site discovery tool to identify regions statistically enriched for RNA editing. FLARE can be configured to analyze any type of RNA editing, including C to U and A to I. We applied FLARE to C-to-U editing data from a RBFOX2-APOBEC1 STAMP experiment, to show that our approach attains high specificity for detecting RBFOX2 binding sites. We also applied FLARE to detect regions of exogenously introduced as well as endogenous A-to-I editing.

Conclusions

FLARE is a fast and flexible workflow that identifies significantly edited regions from RNA-seq data. The FLARE codebase is available at https://github.com/YeoLab/FLARE.
Reliability and validity of the Chinese version of the trauma-specific frailty index (TSFI) for geriatric trauma patients
Authors: Bai Ding-Xi , Liang Yun , Wu Chen‐Xi , Hou Chao-ming , Gao Jing
Published: October 2023

Background

Pre-traumatic frailty in geriatric trauma patients has caught attention from emergency medical workers and the assessment of it thus become one of the important aspects of risk management. Several tools are available to identify frailty, but limited tools have been validated for geriatric trauma patients in China to assess pre-traumatic frailty.The aim of this study is to translate the Trauma-Specific Frailty Index(TSFI) into Chinese, and to evaluate the reliability and validity of the translated version in geriatric trauma patients.

Methods

A cross-sectional study was conducted. The TSFI was translated with using the Brislin model, that included forward and backward translation. A total of 184 geriatric trauma patients were recruited by a convenience sampling between October and December 2020 in Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan. Using reliability or internal consistency tests assessed with Cronbach’s alpha coefficient, split-half reliability and test-retest reliability. Content validity and construct validity analysis were both performed. Sensitivity, specificity and maximum Youden index(YI) were used to determine the optimal cut-off value. The screening performance was examined by Kappa value.

Results

The total study population included 184 subjects, of which 8 participants were excluded, resulting in a study sample size of 176 elderly trauma patients (the completion rate was 95.7%). The Chinese version of Trauma-Specific Frailty Index(C-TSFI) have 15 items with 5 dimensions. Cronbach’s alpha coefficient of the C-TSFI was 0.861, Cronbach’s alpha coefficient of dimensions ranged from 0.837 to 0.875, the split-half reliability of the C-TSFI were 0.894 and 0.880 respectively, test-retest reliability ranged from 0.692 to 0.862. The correlation coefficient between items and the C-TSFI ranged from 0.439 to 0.761. The content validity index for items (I-CVI) of the C-TSFI scale was 0.86~1.00, and the scale of content validity index (S-CVI) was 0.93. The area under curve (AUC) of the C-TSFI was 0.932 (95%CI 0.904–0.96, P < 0.05), the maximum YI was 0.725, the sensitivity was 80.2%, the specificity was 92.3%, and the critical value was 0.31. Kappa value was 0.682 (P < 0.05).

Conclusions

The Chinese version of TSFI could be used as a general assessment tool in geriatric trauma patients, and both its reliability and validity have been demonstrated.
Comparison between available early antiviral treatments in outpatients with SARS-CoV-2 infection: a real-life study
Authors: Rinaldi Matteo , Campoli Caterina , Gallo Mena , Marzolla Domenico , Zuppiroli Alberto , Riccardi Riccardo , Casarini Martina , Riccucci Daniele , Malosso Marta , Bonazzetti Cecilia , Pascale Renato , Tazza Beatrice , Pasquini Zeno , Marconi Lorenzo , Curti Stefania , Giannella Maddalena , Viale Pierluigi
Published: October 2023

Purpose

To investigate the clinical impact of three available antivirals for early COVID-19 treatment in a large real-life cohort.

Methods

Between January and October 2022 all outpatients tested positive for SARS-CoV-2 referring to IRCCS S. Orsola hospital treated with an early antiviral therapy were enrolled. A comparison between patients treated with nirmatrelvir/ritonavir (NTV/r), molnupiravir (MPV) and remdesivir (RDV) was conducted in term of indications and outcome. To account for differences between treatment groups a propensity score analysis was performed. After estimating the weights, we fitted a survey-weighted Cox regression model with inverse-probability weighting with hospital admission/death versus clinical recovery as the primary outcome.

Results

Overall 1342 patients were enrolled, 775 (57.8%), 360 (26.8%) and 207 (15.4%) in MPV, NTV/r and RDV group, respectively. Median age was 73 (59–82) years, male sex was 53.4%. Primary indication was immunosuppression (438, 32.6%), the median time from symptom onset to drug administration was 3 [2–4] days. Overall, clinical recovery was reached in 96.9% of patients, with hospital admission rate of 2.6%. No significant differences were found in clinical recovery nor hospitalization. Cox regression showed a decreased probability of hospital admission/ death among prior vaccinated patients compared with unvaccinated (HR 0.31 [95%CI 0.14–0.70], p = 0.005]). No difference in hospitalization rates in early treatment compared to late treatment were found.

Conclusions

No differences among MPV, NTV/r and RDV in terms of clinical recovery or hospitalization were found. Patients not vaccinated had a significant increased risk of hospitalization.
Outcome and characteristics of nonsecretory multiple myeloma compared with secretory multiple myeloma: a retrospective multicenter study from China
Authors: Sun Hailu , Liu Aijun , Liu Lihong , Wang Wei , Cai Zhen , Yan Hua , Chen Lijuan , Gao Guangxun , Wang Fang , Liao Aijun , Chen Bing , Feng Jia , Li Juan , Huang Dong-Ping , Gao Da , Zhang Qi-Ke , Luo Jun , Fu Rong , Du Juan , Lu Jin
Published: October 2023

Background

Nonsecretory multiple myeloma (NSMM) is a rare type of multiple myeloma (MM). Few studies have described the clinical features and outcomes of NSMM in novel agents. Additionally, the prognostic characteristics have remained controversial in recent years.

Purpose

To investigate the clinical and prognostic features of NSMM and explore the prognostic value of involved free light chain (FLC) levels in NSMM patients in the Chinese population.

Methods

We retrospectively enrolled 176 newly diagnosed NSMM cases between January 2005 and December 2021 from 19 clinical centers in China. The control group was selected using a 1:4 propensity score matching technique of newly diagnosed secretory MM, with age, sex and diagnosis time as the matching variables.

Results

The median age of NSMM patients was 60 years, and 22.6% of patients were classified as ISS stage 3. The ORR of the NSMM patients was 87.4%, and the CR was 65.8%. Compared to the matched secretory MM patients, more NSMM patients achieved CR after first-line treatment (65.8% vs. 36%, p = 0.000). The ORR of first-line treatment was not significantly different between NSMM and secretory MM (89.45% vs. 84.7%, p = 0.196). The first-line PFS was 27.5 m and 23 m (p = 0.063), and the median OS was 81 m and 70 months (p = 0.401). However, for CR-achieved NSMM and CR-not-achieved NSMM patients, the median PFS was 37 m vs. 16 m (p = 0.021), while the median OS showed no difference (107 m vs. 87 m, p = 0.290). In multivariate analysis, the significant factors for PFS were age ≥ 65 and ISS-3. ISS-3 was the only independent prognostic factor of OS. The iFLC ≥ 50 mg/L group had a high ORR of 97.3%, and the median PFS and OS were 48 m and NR, respectively. Compared to the matched secretory MM, the iFLC ≥ 50 mg/L group also showed more CR and longer OS (NR vs. 70 m, p = 0.006) and PFS (48 m vs. 23 m, p = 0.003).

Conclusions

Our results revealed that Chinese NSMM patients are younger and have a higher CR but not superior survival. The subgroup of NSMM patients with iFLC ≥ 50 mg/L had better outcomes than secretory MM.
Online information acquisition affects food risk prevention behaviours: the roles of topic concern, information credibility and risk perception
Authors: You Zhenwu , Zhan Weizhen , Zhang Fan
Published: October 2023

Background

The COVID-19 pandemic has not only brought great challenges to the global health system but also bred numerous rumours about food safety. Food safety issues have once again attracted public attention.

Methods

The data were drawn from the fifth wave of the first Taiwan Communication Survey database. The respondents were selected via multistage stratified random sampling. The sampling units were townships/districts, villages/neighbourhoods and households. The sample consisted of 2098 respondents. This study first used propensity value matching to analyse the direct impact of online food safety information acquisition on preventive behaviours and examined the heterogeneous impact caused by the difference in the degree of topic attention through value matching. Hayes’ PROCESS macro model 6 was applied to confirm the mediating effect and the serial mediating effect.

Results

The research results show that an increase in the frequency of the acquisition of online food safety information significantly increases individuals’ food risk prevention behaviour. However, only users with high concern about the issue are affected. The food risk prevention behaviour of users with low concern about this issue is not affected by the acquisition of online food safety information. Further analysis shows that risk perception and information credibility both play mediating roles in the impact of online food safety information acquisition on food risk prevention behaviour. Moreover, the transmission and united effects of information credibility and risk perception play a distal mediating role.

Conclusions

Food risk prevention behaviours are an important topic for personal health as well as government management. Our study’s findings can provide empirical evidence for risk managers and decision-makers to reevaluate the role of the internet in food risk management.
Validating a measure for eco-anxiety in Portuguese young adults and exploring its associations with environmental action
Authors: Sampaio Francisco , Costa Tiago , Teixeira-Santos Luísa , de Pinho Lara Guedes , Sequeira Carlos , Luís Sílvia , Loureiro Ana , Soro Jerônimo C. , Roldán Merino Juan , Moreno Poyato Antonio , Peña Loray Juan Segundo , Rodríguez Quiroga Andrea , O’Brien Léan V. , Hogg Teaghan L. , Stanley Samantha K.
Published: October 2023

Background

Worsening environmental conditions may amplify people’s emotional responses to an environmental crisis (eco-anxiety). In Portugal, young people seem to be especially concerned about climate change. However, this phenomenon needs to be interpreted using accurate instruments. Thus, this study aimed to validate the Portuguese version of the Hogg Eco-Anxiety Scale (HEAS) in young adults and examine the associations among eco-anxiety, sociodemographic characteristics, and pro-environmental behaviours.

Methods

A survey was administered to 623 Portuguese university students aged between 18 and 25 years. The survey included our Portuguese translation of the HEAS (obtained through a back-translation and pretesting process), a sociodemographic assessment, and questions related to pro-environmental behaviours. Confirmatory factor analysis was conducted to assess the construct validity of the Portuguese version of the HEAS, and global fit indices were used to assess whether the original four-dimensional structure of the scale was reproduced. The reliability of the Portuguese version of the HEAS was evaluated by Cronbach’s alpha and the intraclass correlation coefficient. Measurement invariance examined sex differences in scale interpretation. Linear regressions were used to detect whether sociodemographic variables predict eco-anxiety and whether eco-anxiety predicts pro-environmental behaviours.

Results

The factorial structure of the original scale was replicated in the Portuguese version of the HEAS, showing good internal consistency, reliability over time and strict invariance between men and women. A higher paternal education level predicted greater eco-anxiety in children. Two dimensions of eco-anxiety—namely, rumination and anxiety about personal impacts on the environment—predicted higher engagement in pro-environmental behaviours.

Conclusions

The translated scale is an appropriate tool to measure eco-anxiety in the Portuguese context and should be used to collect evidence to drive environmental and health policies. An individual’s education level should be considered a determinant of their emotional response to environmental conditions. Importantly, eco-anxiety can act as a protective emotional response to preserving the planet.
Study on proximal humerus evaluation of effective treatment (SPHEER) – what is the effect of rehabilitation compliance on clinical outcomes of proximal humerus fractures
Authors: Nah Ming Foo Kenneth , Pereira Michelle Jessica , Hemaavathi Mani , Wong Shiyun Winnie , Lim Chien Joo , Tan Bryan Yijia
Published: October 2023

Introduction

Proximal humeral fractures (PHFs) are 3rd commonest fragility fractures and cause significant functional impairment. This paper sought to determine impact of rehabilitation compliance on the clinical outcomes for non-surgically managed PHFs, while ascertaining reasons for non-compliance which can be addressed to improve compliance.

Methods

Prospective cohort study of patients undergoing non-surgical treatment for PHFs from August 2017 to April 2020 in a tertiary trauma centre was performed. Data was collected via questionnaire: patient demographic data, PHF injury details, clinical outcome measures, therapist-reported (Sport Injury Rehabilitation Adherence Scale [SIRAS]) and patient-reported (subjective compliance, frequency of exercise) rehabilitation compliance measures. Data was analysed using multiple linear regression model to account for confounding variables.

Results

107 participants attended physical therapy follow-up for mean 137.8 days. 6-week SIRAS strongly predicted 3-month Constant score (p = 0.023; 95%CI = 0.265,3.423), OSS (p = 0.038; 95%CI = 0.049,1.634), flexion ROM (p < 0.001; 95%CI = 2.872,8.982), extension ROM (p = 0.035; 95%CI = 0.097,2.614), abduction ROM (p = 0.002;95%CI = 1.995,8.466) and achievement of functional active ROM at 3-months (p = 0.049; 95%CI = 1.001,1.638). Pain was the top reason impairing rehabilitation compliance from therapist (43.9% at 6-weeks and 20.6% at 3-months) and patient-perspective (33.6% at 6-weeks, 24.3% at 3-months). Author-developed patient-reported compliance measures had good correlation with validated SIRAS score (subjective compliance: p < 0.001 frequency of exercise: p = 0.001).

Conclusion

Rehabilitation compliance predicts short-term clinical outcomes up to 3-months and potentially 1-year outcomes. Pain control should be optimised to maximise rehabilitation compliance and improve PHF outcomes. There is lack of consensus definition for rehabilitation compliance measures; patient-reported measures used have good correlation to existing validated measures and could serve as a steppingstone for further research.

Level of evidence

II, cohort study.
Outcomes of direct anterior approach for uncemented total hip replacement in medial femoral neck fractures: a retrospective comparative study on the first 100 consecutive patients
Authors: Di Martino Alberto , Pederiva Davide , Brunello Matteo , Tassinari Leonardo , Geraci Giuseppe , Stefanini Niccolò , Faldini Cesare
Published: October 2023

Background

With the aging of the population, the incidence of medial femoral neck fractures is likely to increase, and along them the need for total hip replacement. The present study aimed to analyze whether the use of the direct anterior hip approach, compared with posterolateral approach in medial proximal femur fracture patients, results in any advantage in terms of complications rate and functional recovery.

Methods

A total of 162 patients were included in the study, and divided by approach: 100 performed with direct anterior approach (group A) and 62 with posterolateral approach (group B). The two populations were overlapping in age (75 vs 74 years; p = 0.13), sex (58F 42M vs 46F 16M; p = 0.12) and BMI (24 vs 24; p = 0.77).

Results

Group A showed a higher ASA score compared to group B (3 vs 2; p = 0.04). Similar hospital stays (7 vs 7 days; p = 0.55) and complication rates (6% vs 8%; p = 0.61) were observed among groups, the most frequent being periprosthetic fractures, and need for allogeneic blood transfusion (20% vs 13%; p = 0.25). Patients in group A (96 vs 85 min; p = 0.10) showed a slightly, longer surgical time and a faster postoperative functional recovery witnessed by the ability to climb stairs at hospital discharge (37% vs 21%; p = 0.041).

Conclusion

The use of the direct anterior hip approach was effective in the management of frail patients with medial femoral neck fractures managed by total hip arthroplasty, allowing faster functional recovery in the elderly population.
Low proviral load in the Kumamoto strain of Japanese Brown cattle infected with the bovine leukemia virus
Authors: Inenaga Toshiaki , Fukuoka Koh , Sumida Mikiya , Aiba Sakiko , Nishikaku Kohei , Matsuno Yuta , Kobayashi Tomoko , Imakawa Kazuhiko
Published: October 2023

Background

The Kumamoto strain of Japanese Brown (JBRK) cattle is a sub-breed of Wagyu and has a different genetic background than that of Japanese Black (JB) cattle. Bovine leukemia virus (BLV) is the pathogen causing enzootic bovine leukosis (EBL), the predominant type of bovine leukosis (BL). EBL is one of the most common bovine infectious diseases in dairy countries, including Japan. Some host genetic factors, including the bovine leukocyte antigen (BoLA)-DRB3 gene, have been associated with the proviral load (PVL) of BLV and/or onset of EBL. Here, we determined the number of BL cases by analyzing prefectural case records in detail. We measured the PVL of BLV-infected JBRK cattle and compared it with that obtained for other major breeds, JB and Holstein-Friesian (HF) cattle. Finally, the relationship between PVL levels and BoLA-DRB3 haplotypes was investigated in BLV-infected JBRK cattle.

Results

We determined the number of BL cases recorded over the past ten years in Kumamoto Prefecture by cattle breed. A limited number of BL cases was observed in JBRK cattle. The proportion of BL cases in the JBRK was lower than that in JB and HF. The PVL was significantly lower in BLV-infected JBRK cattle than that in the JB and HF breeds. Finally, in BLV-infected JBRK cattle, the PVL was not significantly affected by BoLA-DRB3 alleles and haplotypes. BoLA-DRB3 allelic frequency did not differ between BLV-infected JBRK cattle with low PVL and high PVL.

Conclusions

To our knowledge, this is the first report showing that BL occurred less in the JBRK population of Kumamoto Prefecture. After BLV-infection, the PVL was significantly lower in JBRK cattle than that in JB and HF breeds. The genetic factors implicated in maintaining a low PVL have yet to be elucidated, but the BoLA-DRB3 haplotypes are likely not involved.