bluuebunny/crossref_metadata_2025 huggingface dataset:
An Exploratory Analysis of the Role of Adipose Characteristics in Fulltime Wheelchair Users’ Pressure Injury History
Authors: Sonenblum Sharon Eve , Measel Megan , Sprigle Stephen H. , Greenhalgh John , Cathcart John McKay
Published: December 2021

Aim:The goals of this study were 1) to identify the relationship between adipose (subcutaneous and intramuscular) characteristics and pressure injury (PrI) history in wheelchair users and 2) to identify subject characteristics, including biomechanical risk, that are related to adipose characteristics.

Materials and Methods:The buttocks of 43 full-time wheelchair users with and without a history of pelvic PrIs were scanned in a seated posture in a FONAR UPRIGHT® MRI. Intramuscular adipose (the relative difference in intensity between adipose and gluteus maximus) and the subcutaneous adipose characteristics (the relative difference in intensity between subcutaneous adipose under and surrounding the ischium) were compared to PrI history and subject characteristics.

Results:Participants with a history of PrIs had different subcutaneous fat (subQF) characteristics than participants without a history of PrIs. Specifically, they had significantly darker adipose under the ischium than surrounding the ischium (subQF effect size = 0.21) than participants without a history of PrIs (subQF effect size = 0.58). On the other hand, only when individuals with complete fat infiltration (n = 7) were excluded did individuals with PrI history have more fat infiltration than those without a PrI history. The presence of spasms (μ intramuscular adipose, 95% CI with spasms 0.642 [0.430, 0.855], without spasms 0.168 [−0.116, 0.452],p= 0.01) and fewer years using a wheelchair were associated with leaner muscle (Pearson Corr = −0.442,p= 0.003).

Conclusion:The results of the study suggest the hypothesis that changes in adipose tissue under the ischial tuberosity (presenting as darker SubQF) are associated with increased biomechanical risk for pressure injury. Further investigation of this hypothesis, and the role of intramuscular fat infiltration in PrI development, may help our understanding of PrI etiology. It may also lead to clinically useful diagnostic techniques that can identify changes in adipose and biomechanical risk to inform early preventative interventions.
A New Nanomaterial Based on Extracellular Vesicles Containing Chrysin-Induced Cell Apoptosis Through Let-7a in Tongue Squamous Cell Carcinoma
Authors: Yang Zhijing , Liu Da , Zhou Hengzong , Tao Boqiang , Chang Lu , Liu Huimin , Luo Haoming , Wang Dongxu , Liu Weiwei
Published: December 2021

Although the therapeutic strategy showed significant improvement, the therapeutic effect was poor on metastases in tongue squamous cell carcinoma (TSCC) which is the most malignant tumor found in the head and neck. Chrysin, similar to the flavonoids, plays an antitumor role by regulating the expression of ncRNAs in many kinds of cancers. Compared to flavonoids, gold nanoparticles (AuNPs) provide a novel insight into inhibiting cancer cell growth via photothermal therapy (PPT) which is irradiated by near-infrared radiation (NIR). However, most flavonoids and AuNPs lack specificity of tumor in vivo. The extracellular vesicles (EVs) which were abundant with ncRNAs are isolated from the cellular supernatant fluid and have the ability to carry drugs or nanoparticles to improve specificity. In the present study, we aimed to synthesize a new nanomaterial based on EVs containing chrysin and analyzed cell apoptosis in TSCC cells. Our results demonstrated that EVs-chrysin were isolated from SCC9 cells that were treated with chrysin. To improve the therapeutic effect, AuNPs were carried by EVs-chrysin (Au-EVs). Compared to BGC823 and HCC-LM3 cells, the uptake of Au-EVs was specific in SCC9 cells. Moreover, Au-EVs combined with NIR enhanced cell apoptosis in TSCC cells. To confirm the role of miRNAs in cell apoptosis, the differentially expressed miRNAs between EVs-Con and EVs-chrysin were screened by RNA-seq. The results revealed that the let-7a-3p family, which acts as the tumor suppressor, was upregulated in EVs-chrysin compared to EVs-Con. Thus, let-7a-3p was screened in the apoptosis pathway that was associated with the p53 protein. Furthermore, compared to the Con group, Au-EVs combined with the NIR group effectively inhibited tumor growth in vivo via increasing the expression of let-7a-3p. Together, as a new nanomaterial, Au-EVs induced cell apoptosis and inhibited tumor growth by regulating let-7a-3p expression in TSCC.
Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide
Authors: Yang Sen , Zheng Xueni , Qian Meng , Wang He , Wang Fei , Wei Yongzhen , Midgley Adam C. , He Ju , Tian Hongyan , Zhao Qiang
Published: December 2021

Artificial small-diameter vascular grafts (SDVG) fabricated from synthetic biodegradable polymers, such as poly(ε-caprolactone) (PCL), exhibit beneficial mechanical properties but are often faced with issues impacting their long-term graft success. Nitric oxide (NO) is an important physiological gasotransmitter with multiple roles in orchestrating vascular tissue function and regeneration. We fabricated a functional vascular graft by electrospinning of nitrate-functionalized poly(ε-caprolactone) that could release NO in a sustained manner via stepwise biotransformation in vivo. Nitrate-functionalized SDVG (PCL/NO) maintained patency following abdominal arterial replacement in rats. PCL/NO promoted cell infiltration at 3-months post-transplantation. In contrast, unmodified PCL SDVG showed slow cell in-growth and increased incidence of neointima formation. PCL/NO demonstrated improved endothelial cell (EC) alignment and luminal coverage, and more defined vascular smooth muscle cell (VSMC) layer, compared to unmodified PCL SDVG. In addition, release of NO stimulated Sca-1+ vascular progenitor cells (VPCs) to differentiate and contribute to rapid luminal endothelialization. Furthermore, PCL/NO inhibited the differentiation of VPCs into osteopontin-positive cells, thereby preventing vascular calcification. Overall, PCL/NO demonstrated enhanced cell ingrowth, EC monolayer formation and VSMC layer regeneration; whilst inhibiting calcified plaque formation. Our results suggested that PCL/NO could serve as promising candidates for improved and long-term success of SDVG implants.
Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials
Authors: Luo Zhen , Gao Yujuan , Duan Zhongyu , Yi Yu , Wang Hao
Published: December 2021

Mitochondria are well known to serve as the powerhouse for cells and also the initiator for some vital signaling pathways. A variety of diseases are discovered to be associated with the abnormalities of mitochondria, including cancers. Thus, targeting mitochondria and their metabolisms are recognized to be promising for cancer therapy. In recent years, great efforts have been devoted to developing mitochondria-targeted pharmaceuticals, including small molecular drugs, peptides, proteins, and genes, with several molecular drugs and peptides enrolled in clinical trials. Along with the advances of nanotechnology, self-assembled peptide-nanomaterials that integrate the biomarker-targeting, stimuli-response, self-assembly, and therapeutic effect, have been attracted increasing interest in the fields of biotechnology and nanomedicine. Particularly, in situ mitochondria-targeted self-assembling peptides that can assemble on the surface or inside mitochondria have opened another dimension for the mitochondria-targeted cancer therapy. Here, we highlight the recent progress of mitochondria-targeted peptide-nanomaterials, especially those in situ self-assembly systems in mitochondria, and their applications in cancer treatments.
Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration
Authors: Chen Jiawen , Sun Tianyu , You Yan , Wu Buling , Wang Xiaofang , Wu Jingyi
Published: December 2021

Stem cells maintain a subtle balance between self-renewal and differentiation under the regulatory network supported by both intracellular and extracellular components. Proteoglycans are large glycoproteins present abundantly on the cell surface and in the extracellular matrix where they play pivotal roles in facilitating signaling transduction and maintaining stem cell homeostasis. In this review, we outline distinct proteoglycans profiles and their functions in the regulation of stem cell homeostasis, as well as recent progress and prospects of utilizing proteoglycans/glycosaminoglycans as a novel glycomics carrier or bio-active molecules in bone regeneration.
Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
Authors: Wang Rui-Qi , Zhao Wei , Yang Hai-Kui , Dong Jia-Mei , Lin Wei-Jie , He Fa-Zhong , Cui Min , Zhou Zhi-Ling
Published: December 2021

Colorectal cancer (CRC) manifests as gastrointestinal tumors with high intratumoral heterogeneity. Recent studies have demonstrated that CRC may consist of tumor cells with different consensus molecular subtypes (CMS). The advancements in single-cell RNA sequencing have facilitated the development of gene regulatory networks to decode key regulators for specific cell types. Herein, we comprehensively analyzed the CMS of CRC patients by using single-cell RNA-sequencing data. CMS for all malignant cells were assigned using CMScaller. Gene set variation analysis showed pathway activity differences consistent with those reported in previous studies. Cell–cell communication analysis confirmed that CMS1 was more closely related to immune cells, and that monocytes and macrophages play dominant roles in the CRC tumor microenvironment. On the basis of the constructed gene regulation networks (GRNs) for each subtype, we identified that the critical transcription factor ERG is universally activated and upregulated in all CMS in comparison with normal cells, and that it performed diverse roles by regulating the expression of different downstream genes. In summary, molecular subtyping of single-cell RNA-sequencing data for colorectal cancer could elucidate the heterogeneity in gene regulatory networks and identify critical regulators of CRC.
Role of Main RNA Methylation in Hepatocellular Carcinoma: N6-Methyladenosine, 5-Methylcytosine, and N1-Methyladenosine
Authors: Xu Yating , Zhang Menggang , Zhang Qiyao , Yu Xiao , Sun Zongzong , He Yuting , Guo Wenzhi
Published: December 2021

RNA methylation is considered a significant epigenetic modification, a process that does not alter gene sequence but may play a necessary role in multiple biological processes, such as gene expression, genome editing, and cellular differentiation. With advances in RNA detection, various forms of RNA methylation can be found, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 5-methylcytosine (m5C). Emerging reports confirm that dysregulation of RNA methylation gives rise to a variety of human diseases, particularly hepatocellular carcinoma. We will summarize essential regulators of RNA methylation and biological functions of these modifications in coding and noncoding RNAs. In conclusion, we highlight complex molecular mechanisms of m6A, m5C, and m1A associated with hepatocellular carcinoma and hope this review might provide therapeutic potent of RNA methylation to clinical research.
Bone Marrow Adipocytes: A Critical Player in the Bone Marrow Microenvironment
Authors: Wang Lipeng , Zhang Hao , Wang Sicheng , Chen Xiao , Su Jiacan
Published: December 2021

Recognized for nearly 100 years, bone marrow adipocytes (BMAs) form bone marrow niches that contain hematopoietic and bone cells, the roles of which have long been underestimated. Distinct from canonical white, brown, and beige adipocytes, BMAs derived from bone marrow mesenchymal stromal cells possess unique characteristics and functions. Recent single-cell sequencing studies have revealed the differentiation pathway, and seminal works support the tenet that BMAs are critical regulators in hematopoiesis, osteogenesis, and osteoclastogenesis. In this review, we discuss the origin and differentiation of BMAs, as well as the roles of BMAs in hematopoiesis, osteogenesis, osteoclastogenesis, and immune regulation. Overall, BMAs represent a novel target for bone marrow-related diseases, including osteoporosis and leukemia.
Spotlight on Isl1: A Key Player in Cardiovascular Development and Diseases
Authors: Ren Jie , Miao Danxiu , Li Yanshu , Gao Rui
Published: December 2021

Cardiac transcription factors orchestrate a regulatory network controlling cardiovascular development. Isl1, a LIM-homeodomain transcription factor, acts as a key player in multiple organs during embryonic development. Its crucial roles in cardiovascular development have been elucidated by extensive studies, especially as a marker gene for the second heart field progenitors. Here, we summarize the roles of Isl1 in cardiovascular development and function, and outline its cellular and molecular modes of action, thus providing insights for the molecular basis of cardiovascular diseases.
Acorenone C: A New Spiro-Sesquiterpene from a Mangrove-Associated Fungus, Pseudofusicoccum sp. J003
Authors: Jia Shujie , Su Xiangdong , Yan Wensi , Wu Meifang , Wu Yichuang , Lu Jielang , He Xin , Ding Xin , Xue Yongbo
Published: December 2021

Mangrove-derived endophytes are rich in bioactive secondary metabolites with a variety of biological activities. Recently, a fungus Pseudofusicoccum sp. J003 was first isolated by our research group from mangrove species Sonneratia apetala Buch.-Ham. The subsequent chemical investigation of the methanol extract of the culture broth of this strain has led to the isolation of a new sesquiterpenoid named acorenone C (1), two alkaloids (2–3), four phenolic compounds (4–7), and four steroid derivatives (8–11). The new structure of 1 was established by extensive spectroscopic analysis, including 1D, 2D NMR spectroscopy, and HRESIMS. Its absolute configuration was elucidated by experimental ECD and ECD calculation. The in vitro AChE inhibitory, anti-inflammatory, and cytotoxic activities of the selected compounds were evaluated. The results showed that compound 1 showed mild AChE inhibitory activity, with an inhibition rate of 23.34% at the concentration of 50 μM. Compound 9 exerted a significant inhibitory effect against nitric oxide (NO) production in LPS-stimulated RAW 264.7 mouse macrophages, with an inhibition rate of 72.89% at the concentration of 25 μM, better than that of positive control L-NMMA. Compound 9 also displayed obvious inhibition effects on the growth of two human tumor cell lines, HL-60 and SW480 (inhibition rates 98.68 ± 0.97% and 60.40 ± 4.51%, respectively). The antimicrobial activities of the compounds (1–11) against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa were also tested; however, none of them showed antimicrobial activities.
Cu-Based Conductive MOF Grown in situ on Cu Foam as a Highly Selective and Stable Non-Enzymatic Glucose Sensor
Authors: Hu Qin , Qin Jie , Wang Xiao-Feng , Ran Guang-Ying , Wang Qiang , Liu Guang-Xiang , Ma Jian-Ping , Ge Jing-Yuan , Wang Hai-Ying
Published: December 2021

A non-enzymatic electrochemical sensor for glucose detection is executed by using a conductive metal–organic framework (MOF) Cu-MOF, which is built from the 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) ligand and copper acetate by hydrothermal reaction. The Cu-MOF demonstrates superior electrocatalytic activity for glucose oxidation under alkaline pH conditions. As an excellent non-enzymatic sensor, the Cu-MOF grown on Cu foam (Cu-MOF/CF) displays an ultra-low detection limit of 0.076 μM through a wide concentration range (0.001–0.95 mM) and a strong sensitivity of 30,030 mA μM−1 cm−2. Overall, the Cu-MOF/CF exhibits a low detection limit, high selectivity, excellent stability, fast response time, and good practical application feasibility for glucose detection and can promote the development of MOF materials in the field of electrochemical sensors.
Quantum Dynamics of Rotational Transitions in CN (X2Σ+) by H+ Collisions
Authors: Anusuri Bhargava , Dhilip Kumar T. J. , Kumar Sanjay
Published: December 2021

Collisional cross-sections of inelastic rotational excitations of CN in its ground electronic state (X2Σ+) by H+ scattering are studied by the exact quantum mechanical close-coupling (CC) method at very low collision energies (0–600 cm−1) relevant to interstellar atmospheres. Ab initio rigid rotor potential energy surface computed at MRCI/cc-pVTZ level of accuracy has been employed. Rate coefficients for the rotational excitations have also been calculated. The obtained results are compared with previous theoretical calculations and analyzed whether proton collisions could be significant sources for rotationally excited CN as a possible source for cosmic microwave background of about 3 K from the interstellar media.
Yap5 Competes With Hap4 for the Regulation of Iron Homeostasis Genes in the Human Pathogen Candida glabrata
Authors: Delaveau Thierry , Thiébaut Antonin , Benchouaia Médine , Merhej Jawad , Devaux Frédéric
Published: December 2021

The CCAAT-binding complex (CBC) is a conserved heterotrimeric transcription factor which, in fungi, requires additional regulatory subunits to act on transcription. In the pathogenic yeast Candida glabrata, CBC has a dual role. Together with the Hap4 regulatory subunit, it activates the expression of genes involved in respiration upon growth with non-fermentable carbon sources, while its association with the Yap5 regulatory subunit is required for the activation of iron tolerance genes in response to iron excess. In the present work, we investigated further the interplay between CBC, Hap4 and Yap5. We showed that Yap5 regulation requires a specific Yap Response Element in the promoter of its target gene GRX4 and that the presence of Yap5 considerably strengthens the binding of CBC to the promoters of iron tolerance genes. Chromatin immunoprecipitation (ChIP) and transcriptome experiments showed that Hap4 can also bind these promoters but has no impact on the expression of those genes when Yap5 is present. In the absence of Yap5 however, GRX4 is constitutively regulated by Hap4, similarly to the genes involved in respiration. Our results suggest that the distinction between the two types of CBC targets in C. glabrata is mainly due to the dependency of Yap5 for very specific DNA sequences and to the competition between Hap4 and Yap5 at the promoter of the iron tolerance genes.
A Review on Host-Leptospira Interactions: What We Know and Future Expectations
Authors: Daroz Brenda B. , Fernandes Luis G. V. , Cavenague Maria F. , Kochi Leandro T. , Passalia Felipe J. , Takahashi Maria B. , Nascimento Filho Edson G. , Teixeira Aline F. , Nascimento Ana L. T. O.
Published: December 2021

Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is considered a neglected infectious disease of human and veterinary concern. Our group has been investigating proteins annotated as hypothetical, predicted to be located on the leptospiral surface. Because of their location, these proteins may have the ability to interact with various host components, which could allow establishment of the infection. These proteins act as adherence factors by binding to host receptor molecules, such as the extracellular matrix (ECM) components laminin and glycosaminoglycans to help bacterial colonization. Leptospira also interacts with the host fibrinolytic system, which has been demonstrated to be a powerful tool for invasion mechanisms. The interaction with fibrinogen and thrombin has been shown to reduce fibrin clot formation. Additionally, the degradation of coagulation cascade components by secreted proteases or by acquired surface plasmin could also play a role in reducing clot formation, hence facilitating dissemination during infection. Interaction with host complement system regulators also plays a role in helping bacteria to evade the immune system, facilitating invasion. Interaction of Leptospira to cell receptors, such as cadherins, can contribute to investigate molecules that participate in virulence. To achieve a better understanding of the host-pathogen interaction, leptospiral mutagenesis tools have been developed and explored. This work presents several proteins that mediate binding to components of the ECM, plasma, components of the complement system and cells, to gather research achievements that can be helpful in better understanding the mechanisms of leptospiral-host interactions and discuss genetic manipulation for Leptospira spp. aimed at protein function validation.
Identification of Novel Malaria Transmission-Blocking Vaccine Candidates
Authors: Takashima Eizo , Tachibana Mayumi , Morita Masayuki , Nagaoka Hikaru , Kanoi Bernard N. , Tsuboi Takafumi
Published: December 2021

Control measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery.
Internalizing CO2-Equivalent Emissions Issued From Agricultural Activities
Authors: Dragicevic Arnaud Zlatko
Published: December 2021

The aim of this article is to consider the market-based instruments, such as the ETS system, for the internalization of the CO2-equivalent emissions issued from the agricultural sector. We use a hypothetical market valuation of the emissions and we extend the analysis to the optional pricing with double barriers. According to our results, the purpose of attaining the levels of carbon emissions recommended by the French public authorities, with a level of reductions down by 50.00% in 2030, could be successful would the terminal range of optional prices stand between 76.35 and 89.56 Eur.
Coordinated Implementation of Climate-Smart Practices in Coffee Farming Increases Benefits at Farm, Landscape and Global Scale
Authors: Schmidt Paul Günter , Bunn Christian
Published: December 2021

Coffee is a major commodity crop that shapes large shares of tropical landscapes. However, the sustainability of these landscapes is threatened by climate change. Whilst adopting climate-smart (CS) practices clearly offers direct benefits to local farmers, their greater benefits at landscape and global scales has not been studied for specific commodity crops so far. Our research uniquely outlines how local adoption of CS-practices in coffee-farming systems provides local, landscape and global benefits. We review literature on CS agriculture, CS landscapes, and coffee farming to firstly identify the different CS-practices applicable to coffee farming systems, and then group these into functional groups that represent the main functional trait targeted by different practices within coffee-farming systems. This allows identifying benefits provided at local, landscape and global scales. The seven functional groups identified are: soil characteristics; water management; crop and genetic diversity; climate buffer and adjustment; crop nutrient management; structural elements and natural habitats; and system functioning. Benefits offered at landscape and global scales (non-exhaustively) include improved water quality, biodiversity conservation and habitat connectivity, as well as stabilized regional climate patterns. Our review shows that regulating services are especially pronounced, although the extent of benefits provided depend on landscape coordination. We discuss considerations for managing possible conflicts, coordinating actions, financing and accommodating lead time. Local farmers, policy-makers and global donors must unite to improve uptake of CS coffee-production practices in a coordinated way, to thereby augment and safeguard coffee-farming's socio-ecological system along with associated local, landscape and global benefits.
The Impact of Socio-Economic Inertia and Restrictions on Net-Negative Emissions on Cost-Effective Carbon Price Pathways
Authors: Hof Andries F. , van der Wijst Kaj-Ivar , van Vuuren Detlef P.
Published: December 2021

Many countries have indicated to plan or consider the use of carbon pricing. Model-based scenarios are used to inform policymakers about emissions pathways and cost-effective carbon prices. Many of these scenarios are based on the Hotelling rule, assuming that a carbon price path increasing with the interest rate leads to a cost-effective strategy. We test the robustness of this rule by using experiments with plausible assumptions for learning by doing, inertia in reducing emissions, and restrictions on net-negative emissions. Analytically, we show that if mitigation technologies become cheaper if their capacities are increased, Hotelling does not always apply anymore. Moreover, the initial carbon price is heavily influenced by restrictions on net-negative emissions and the pathway by both restrictions on net-negative emissions and socio-economic inertia. This means that Hotelling pathways are not necessarily optimal: in fact, combining learning by doing and the above restrictions leads to initial carbon prices that are more than twice as high as a Hotelling pathway and thus to much earlier emission reductions. The optimal price path also increases less strongly and may even decline later in the century, leading to higher initial abatement costs but much lower long-term costs.
Hsa_circ_0003204 Knockdown Weakens Ox-LDL-Induced Cell Injury by Regulating miR-188-3p/TRPC6 Axis in Human Carotid Artery Endothelial Cells and THP-1 Cells
Authors: Peng Wenjia , Li Shuai , Chen Shiyue , Yang Jiacheng , Sun Ze
Published: December 2021

Background: Circular RNAs (circRNAs) are involved in atherosclerosis (AS) development. However, the function and mechanism of circRNA hsa_circ_0003204 (circ_0003204) in carotid artery AS remain unclear.

Methods: Oxidized low-density lipoprotein (ox-LDL)-treated human carotid artery endothelial cells (HCtAECs) and THP-1 cells were used as cell models of carotid artery AS. Relative levels of circ_0003204, microRNA-188-3p (miR-188-3p), and transient receptor potential canonical channel 6 (TRPC6) were detected by quantitative reverse transcription–polymerase chain reaction or Western blotting. The targeting relationship between circ_0003204 or TRPC6 and miR-188-3p was assessed via dual-luciferase reporter analysis and RNA immunoprecipitation. Cell proliferation was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was analyzed via assessing cell caspase-3 activity, apoptosis, and apoptosis-related protein. Inflammatory response was analyzed via analysis of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Oxidative stress was assessed via determination of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD).

Results: Circ_0003204 and TRPC6 levels were elevated, and miR-188-3p expression declined in ox-LDL-treated HCtAECs and THP-1 cells. Circ_0003204 could regulate TRPC6 expression via mediating miR-188-3p. Circ_0003204 silencing weakened ox-LDL-induced viability inhibition and apoptosis in HCtAECs, and inflammatory response and oxidative stress in THP-1 cells via regulating miR-188-3p. MiR-188-3p overexpression attenuated ox-LDL-induced injury in HCtAECs and THP-1 cells by targeting TRPC6.

Conclusion: Circ_0003204 knockdown mitigated ox-LDL-induced injury in HCtAECs and THP-1 cells via regulating the miR-188-3p/TRPC6 axis, indicating that circ_0003204 might play an important role in carotid artery AS.
Cardiorespiratory Polygraphy for Detection of Obstructive Sleep Apnea in Patients With Atrial Fibrillation
Authors: Delesie Michiel , Knaepen Lieselotte , Verbraecken Johan , Weytjens Karolien , Dendale Paul , Heidbuchel Hein , Desteghe Lien
Published: December 2021

Background: Obstructive sleep apnea (OSA) is a modifiable risk factor of atrial fibrillation (AF) but is underdiagnosed in these patients due to absence of good OSA screening pathways. Polysomnography (PSG) is the gold standard for diagnosing OSA but too resource-intensive as a screening tool. We explored whether cardiorespiratory polygraphy (PG) devices using an automated algorithm for Apnea-Hypopnea Index (AHI) determination can meet the requirements of a good screening tool in AF patients.

Methods: This prospective study validated the performance of three PGs [ApneaLink Air (ALA), SOMNOtouch RESP (STR) and SpiderSAS (SpS)] in consecutive AF patients who were referred for PSG evaluation. Patients wore one of the three PGs simultaneously with PSG, and a different PG during each of three consecutive nights at home. Severity of OSA was classified according to the AHI during PSG (<5 = no OSA, 5–14 = mild, 15–30 = moderate, >30 = severe).

Results: Of the 100 included AF patients, PSG diagnosed at least moderate in 69% and severe OSA in 33%. Successful PG execution at home was obtained in 79.1, 80.2 and 86.8% of patients with the ALA, STR and SpS, respectively. For the detection of clinically relevant OSA (AHI ≥ 15), an area under the curve of 0.802, 0.772 and 0.803 was calculated for the ALA, STR and SpS, respectively.

Conclusions: This study indicates that home-worn PGs with an automated AHI algorithm can be used as OSA screening tools in AF patients. Based on an appropriate AHI cut-off value for each PG, the device can guide referral for definite PSG diagnosis.
Depositional Model for Turbidite Lobes in Complex Slope Settings Along Transform Margins: The Motta San Giovanni Formation (Miocene—Calabria, Italy)
Authors: Rohais Sébastien , Bailleul Julien , Brocheray Sandra , Schmitz Julien , Paron Paolo , Kezirian Francis , Barrier Pascal
Published: December 2021

Intraslope lobes, or perched lobes, are attracting scientific interest because they represent a key archive between the shelf and the deep basin plain when looking at a complete source-to-sink depositional system across a continental margin and can form significant offshore hydrocarbon plays. In this study, we focus on a detailed characterization of intraslope lobes of the Motta San Giovanni Formation (Miocene, Calabria), which were deposited in confined conditions during the Miocene along a transform margin. We determine the typical facies associations and stratigraphic architecture of these intraslope lobes using a 3D digital outcrop model resulting from a combined Uncrewed Aerial Vehicle (UAV) and walking acquisition, together with sedimentological logging and geological mapping. We propose recognition criteria for the identification of intraslope lobes, including facies and geometries, integrated within a depositional model. A comparison with other well-known intraslope and confined lobes, as well as basin floor lobes, is finally discussed, to highlight the peculiarities of intraslope lobes deposited along transform margins. The diagnostic depositional model for these types of intraslope lobes includes four main stages of evolution: 1) Stage 1—isolated detached lobe precursor in response to a flushed hydraulic jump, 2) Stage 2—prograding and aggrading lobe elements associated with a relatively stable and submerged hydraulic jump in the Channel-Lobe Transition Zone (CLTZ), 3) Stage 3—major bypass associated with lateral accretion and local aggradation interpreted as a renewal of a normal hydraulic jump in the CTLZ, and 4) Stage 4—erosion and bypass then abandonment. The development of intraslope lobes along active transform margins is allowed by tectonically induced slope segmentation and local confinement. In such a context, flow stripping and overspill processes occurred. Resulting lobes appear to be particularly small and relatively thin sandy deposits. They could be considered end-member in a lobe classification based on the Net-to-Gross content (high) and taking into account their thickness/width ratio (intermediate between 10:1 and 100:1 lines).
Aberrant Gut-To-Brain Signaling in Irritable Bowel Syndrome - The Role of Bile Acids
Authors: Ní Dhonnabháín Róisín , Xiao Qiao , O’Malley Dervla
Published: December 2021

Functional bowel disorders such as irritable bowel syndrome (IBS) are common, multifactorial and have a major impact on the quality of life of individuals diagnosed with the condition. Heterogeneity in symptom manifestation, which includes changes in bowel habit and visceral pain sensitivity, are an indication of the complexity of the underlying pathophysiology. It is accepted that dysfunctional gut-brain communication, which incorporates efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones and local paracrine and neurocrine factors, such as host and microbially-derived signaling molecules, underpins symptom manifestation. This review will focus on the potential role of hepatic bile acids in modulating gut-to-brain signaling in IBS patients. Bile acids are amphipathic molecules synthesized in the liver, which facilitate digestion and absorption of dietary lipids. They are also important bioactive signaling molecules however, binding to bile acid receptors which are expressed on many different cell types. Bile acids have potent anti-microbial actions and thereby shape intestinal bacterial profiles. In turn, bacteria with bile salt hydrolase activity initiate the critical first step in transforming primary bile acids into secondary bile acids. Individuals with IBS are reported to have altered microbial profiles and modified bile acid pools. We have assessed the evidence to support a role for bile acids in the pathophysiology underlying the manifestation of IBS symptoms.
Structured Reporting of Computed Tomography in the Staging of Neuroendocrine Neoplasms: A Delphi Consensus Proposal
Authors: Granata Vincenza , Coppola Francesca , Grassi Roberta , Fusco Roberta , Tafuto Salvatore , Izzo Francesco , Reginelli Alfonso , Maggialetti Nicola , Buccicardi Duccio , Frittoli Barbara , Rengo Marco , Bortolotto Chandra , Prost Roberto , Lacasella Giorgia Viola , Montella Marco , Ciaghi Eleonora , Bellifemine Francesco , De Muzio Federica , Danti Ginevra , Grazzini Giulia , De Filippo Massimo , Cappabianca Salvatore , Barresi Carmelo , Iafrate Franco , Stoppino Luca Pio , Laghi Andrea , Grassi Roberto , Brunese Luca , Neri Emanuele , Miele Vittorio , Faggioni Lorenzo
Published: December 2021

Background

Structured reporting (SR) in radiology is becoming increasingly necessary and has been recognized recently by major scientific societies. This study aims to build structured CT-based reports in Neuroendocrine Neoplasms during the staging phase in order to improve communication between the radiologist and members of multidisciplinary teams.

Materials and Methods

A panel of expert radiologists, members of the Italian Society of Medical and Interventional Radiology, was established. A Modified Delphi process was used to develop the SR and to assess a level of agreement for all report sections. Cronbach’s alpha (Cα) correlation coefficient was used to assess internal consistency for each section and to measure quality analysis according to the average inter-item correlation.

Results

The final SR version was built by including n=16 items in the “Patient Clinical Data” section, n=13 items in the “Clinical Evaluation” section, n=8 items in the “Imaging Protocol” section, and n=17 items in the “Report” section. Overall, 54 items were included in the final version of the SR. Both in the first and second round, all sections received more than a good rating: a mean value of 4.7 and range of 4.2-5.0 in the first round and a mean value 4.9 and range of 4.9-5 in the second round. In the first round, the Cα correlation coefficient was a poor 0.57: the overall mean score of the experts and the sum of scores for the structured report were 4.7 (range 1-5) and 728 (mean value 52.00 and standard deviation 2.83), respectively. In the second round, the Cα correlation coefficient was a good 0.82: the overall mean score of the experts and the sum of scores for the structured report were 4.9 (range 4-5) and 760 (mean value 54.29 and standard deviation 1.64), respectively.

Conclusions

The present SR, based on a multi-round consensus-building Delphi exercise following in-depth discussion between expert radiologists in gastro-enteric and oncological imaging, derived from a multidisciplinary agreement between a radiologist, medical oncologist and surgeon in order to obtain the most appropriate communication tool for referring physicians.
Long-Term Physical Activity Participation and Subsequent Incident Type 2 Diabetes Mellitus: A Population-Based Cohort Study
Authors: Li Chenglong , Ma Yanjun , Hua Rong , Zheng Fanfan , Xie Wuxiang
Published: December 2021

Background

Uncertainty remains concerning association between long-term physical activity and incident type 2 diabetes mellitus (DM). We intended to evaluate physical activity participation over a 6-year span and assess association with subsequent 10-year incident DM risk, as well as examine mediation role by obesity.

Methods

A total of 9757 community-dwelling adults aged ≥ 50 years in England were included in the population-based cohort. Physical activity participation, including trajectories and cumulative participation were assessed using weighted Z score over a 6-year span from wave 1 (2002–2003) to wave 4 (2008–2009). Incident DM recorded over a 10-year span from wave 4 (2008–2009) to wave 9 (2018–2019) was outcome.

Results

5 distinct activity trajectories were identified, including persistently low (N=3037, incident DM=282), initially low then improving (1868, 90), initially high then declining (325, 20), persistently moderate (2489, 170), and persistently high (2038, 108). Compared with persistently low, participants of initially low then improving, persistently moderate and high were associated with lower incident DM risk, with multivariable-adjusted hazard ratios (HR) of 0.41 (95% confidence interval [CI]: 0.32 to 0.53, P<0.001), 0.70 (95% CI: 0.56 to 0.89, P=0.004) and 0.49 (95% CI: 0.37 to 0.65, P <0.001), respectively. Elevated cumulative activity was also associated with lower DM risk, with each quintile increment in cumulative weighted Z score corresponding to HR of 0.76 (95% CI: 0.71 to 0.82, P <0.001). Mediation analysis found that body mass index, waist circumference and change in body mass index mediate 10% (P <0.001), 17% (P <0.001) and 9% (P <0.001) of the observed association between activity and incident DM, respectively.

Conclusions

For middle aged and older adults, both gradually improved and persistently active participation in physical activity were associated with subsequent lower risk of incident DM, with obesity playing a potential mediator. Strategies focusing on improving and maintaining active participation in physical activity might be beneficial from DM prevention perspective.
Effects of Pituitary Surgery and High-Dose Cabergoline Therapy on Metabolic Profile in Patients With Prolactinoma Resistant to Conventional Cabergoline Treatment
Authors: Pirchio Rosa , Auriemma Renata S. , Solari Domenico , Arnesi Mauro , Pivonello Claudia , Negri Mariarosaria , de Angelis Cristina , Cavallo Luigi M. , Cappabianca Paolo , Colao Annamaria , Pivonello Rosario
Published: December 2021

Objective

Control of prolactin excess is associated with the improvement in gluco-insulinemic and lipid profile. The current study aimed at investigating the effects of pituitary surgery and medical therapy with high dose cabergoline (≥2mg/week) on metabolic profile in patients with prolactinoma resistant to cabergoline conventional doses (<2mg/week).

Design

Thirty-four patients (22 men, 12 women, aged 33.9 ± 12.5 years) with prolactinoma (4 microadenomas and 30 macroadenomas) were included in the present study. Among them 17 (50%) received pituitary surgery (PS, Group1) and 17 (50%) medical therapy with high dose cabergoline (Group 2).

Methods

In the whole patient cohort, anthropometric (weight, BMI) and biochemical (fasting glucose and insulin, triglycerides, total, HDL and LDL-cholesterol, HOMA-IR, HOMA-β and ISI0) parameters were evaluated before and within 12 months after treatment.

Results

In Group 1, prolactin (p=0.002), total cholesterol (p=0.012), and triglycerides (p=0.030) significantly decreased after pituitary surgery compared to the baseline. Prolactin significantly correlated with fasting glucose (r=0.056, p=0.025). In Group 2, fasting insulin (p=0.033), HOMA-β (p=0.011) and ISI0 (p=0.011) significantly improved compared to baseline. Postoperative cabergoline dose significantly correlated with Δfasting glucose (r=-0.556, p=0.039) and ΔLDL cholesterol (r=- 0.521, p=0.046), and was the best predictor of ΔLDL cholesterol (r2 = 0.59, p=0.002) in Group 1.

Conclusions

The rapid decrease in PRL levels induced by PS might improve lipid metabolism, whereas HD-CAB might exert a beneficial impact on both insulin secretion and peripheral sensitivity, thus inducing a global metabolic improvement.
Substance Use Affects Type 1 Diabetes Pancreas Pathology: Implications for Future Studies
Authors: Bruggeman Brittany S. , Campbell-Thompson Martha , Filipp Stephanie L. , Gurka Matthew J. , Atkinson Mark A. , Schatz Desmond A. , Jacobsen Laura M.
Published: December 2021

Access to human pancreas samples from organ donors has greatly advanced our understanding of type 1 diabetes pathogenesis; however, previous studies have shown that donors have a high rate of substance use, and its impact on pancreatic histopathology in this disease is not well described. One-hundred-thirty-one type 1 diabetes and 111 control organ donor pancreata from persons 12-89 years of age (mean 29.8 ± 15.5 years) within the Network for Pancreatic Organ donors with Diabetes (nPOD) were examined for insulin positivity, insulitis, amyloid staining, acute and chronic pancreatitis, and chronic exocrine changes (acinar atrophy, fibrosis, fatty infiltration, or periductal fibrosis); findings were compared by history of substance use. A secondary analysis compared exocrine pancreatic histopathologic findings in type 1 diabetes versus control organ donors regardless of substance use history. We observed a high but congruent rate of substance use in type 1 diabetes and control organ donors (66.4% and 64% respectively). Among donors with type 1 diabetes (but not controls), islet amyloid (OR 9.96 [1.22, 81.29]) and acute pancreatitis (OR 3.2 [1.06, 9.63]) were more common in alcohol users while chronic exocrine changes (OR 8.86 [1.13, 69.31]) were more common in cocaine users. Substance use impacted the pancreata of donors with type 1 diabetes more than controls. Overall, despite similar rates of substance use, acute pancreatitis (15.3% versus 4.5%, p=0.0061), chronic pancreatitis (29.8% versus 9.9%, p=0.0001), and chronic exocrine changes (73.3% versus 36.9%, p<0.0001) were more common in type 1 diabetes donors than controls. Alcohol and/or cocaine use in type 1 diabetes organ donors increases exocrine pancreas pathology and islet amyloid deposition but does not affect insulitis or insulin positivity. Exocrine pathology in type 1 diabetes donors is common, and further study of the pathophysiology of these changes is needed.
Do East Asians With Normal Glucose Tolerance Have Worse β-Cell Function? A Meta-Analysis of Epidemiological Studies
Authors: Li Li , Zou Xiantong , Huang Qi , Han Xueyao , Zhou Xianghai , Ji Linong
Published: December 2021

Background

The difference in the relationship between β-cell function and insulin resistance among Africans, Caucasians and East Asians with normal glucose tolerance (NGT) was not well investigated.

Methods

We searched PubMed and Web of Science with keywords and identified studies that used the homeostasis model assessment (HOMA) model to evaluate β-cell function (HOMA-B) and insulin sensitivity/resistance (HOMA-S/HOMA-IR) in certain ethnic groups. We used random-effect model to pool data of HOMAs and compared the combined data among the three ethnic groups using subgroup analysis. Linear regression analysis was used to estimate the coefficient of HOMA-S on HOMA-B in these ethnic groups.

Results

We evaluated pooled data of HOMAs in eight African, 26 Caucasian, and 84 East Asian cohorts with NGT, and also 2,392, 6,645 and 67,317 individuals, respectively. The three ethnic groups had distinct HOMA-B but similar HOMA-IR. The regression coefficient of lnHOMA-B on lnHOMA-S was different between Africans and Caucasians (−1.126 vs −0.401, P = 0.0006) or East Asian (−1.126 vs −0.586, P = 0.0087), but similar between Caucasians and East Asians (−0.401 vs −0.586, P = 0.1282). The coefficient in all ethnic groups was similar when age, BMI, and gender were adjusted (African vs Caucasian P = 0.0885, African vs East Asian P = 0.1092, and Caucasian vs East Asian P = 0.6298).

Conclusions

In subjects with NGT, East Asians had lower HOMA-B but similar β-cell response relative to insulin resistance with Caucasians and Africans when age, BMI, and gender were controlled. This result may challenge the allegation that there was an Asian-specific diabetes phenotype with worse β-cell function.
Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [64Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial
Authors: Jensen Jacob K. , Zobel Emilie H. , von Scholten Bernt J. , Rotbain Curovic Viktor , Hansen Tine W. , Rossing Peter , Kjaer Andreas , Ripa Rasmus S.
Published: December 2021

Background

Quantification of coronary artery inflammation and atherosclerosis remains a challenge in high-risk individuals. In this study we sought to investigate if the glucagon like peptide-1 receptor agonist liraglutide has a direct anti-inflammatory effect in the coronary arteries using positron emission tomography (PET) with a radioactive tracer targeting activated macrophages in the vessel-wall.

Methods

Thirty randomly selected participants with type 2 diabetes from the placebo-controlled trial LIRAFLAME were enrolled in this sub-study. Participants were, prior to enrollment in this sub-study, randomized to either treatment with daily liraglutide (n=15) or placebo (n=15). Both groups underwent a combined [64Cu]Cu-DOTATATE positron emission tomography and computed tomography scan of the heart at baseline and after 26 weeks of treatment. Coronary artery uptake of [64Cu]Cu-DOTATATE were measured as maximum standardized uptake values (SUVmax); and means of the maximum values (mSUVmax), both values were calculated at the level of each participant and each individual coronary-segment.

Results

SUVmax and mSUVmax values decreased significantly in the liraglutide group both at the participant level (SUVmax: p=0.013; mSUVmax: p=0.004) and at the coronary-segment level (SUVmax: p=0.001; mSUVmax: p<0.0001). No change was observed in the placebo group neither at the participant level (SUVmax: p=0.69; mSUVmax: p=0.67) or at the coronary-segment level (SUVmax: p=0.49; mSUVmax: p=0.30). When comparing the mean change in uptake values between the two groups at both the participant level (SUVmax: p=0.076; mSUVmax: p=0.077) and the coronary segment level (SUVmax: p=0.13; mSUVmax: p=0.11) a borderline significant difference was observed. Baseline SUVmax [64Cu]Cu-DOTATATE uptake values showed a weak positive correlation with the inflammatory biomarker high-sensitivity c-reactive protein (τ =0.26, p=0.045).

Conclusion

Liraglutide treatment for 26-weeks caused a significant reduction in [64Cu]Cu-DOTATATE uptake in the coronary arteries whereas this was not seen in the placebo treated group. In addition, [64Cu]Cu-DOTATATE PET/CT as a marker of coronary inflammation correlated with the systemic inflammation marker hs-CRP.